o-(2-fluoroethyl)tyrosine and Brain-Neoplasms

In recent years, PET using radiolabelled amino acids has gained considerable interest as an additional tool besides MRI to improve the diagnosis of cerebral gliomas and brain metastases. A very successful tracer in this field is O-(2-[18F]fluoroethyl)-L-tyrosine (FET) which in recent years has replaced short-lived tracers such as [11C]-methyl-L-methionine in many neuro-oncological centers in Western Europe. FET can be produced with high efficiency and distributed in a satellite concept like 2- [18F]fluoro-2-deoxy-D-glucose. Many clinical studies have demonstrated that FET PET provides important diagnostic information regarding the delineation of cerebral gliomas for therapy planning, an improved differentiation of tumor recurrence from treatment-related changes and sensitive treatment monitoring. In parallel, a considerable number of experimental studies have investigated the uptake mechanisms of FET on the cellular level and the behavior of the tracer in various benign lesions in order to clarify the specificity of FET uptake for tumor tissue. Further studies have explored the effects of treatment related tissue alterations on tracer uptake such as surgery, radiation and drug therapy. Finally, the role of blood-brain barrier integrity for FET uptake which presents an important aspect for PET tracers targeting neoplastic lesions in the brain has been investigated in several studies. Based on a literature research regarding experimental FET studies and corresponding clinical applications this article summarizes the knowledge on the uptake behavior of FET, which has been collected in more than 30 experimental studies during the last two decades and discusses the role of these results in the clinical context.

Topics: Animals; Biological Transport; Blood-Brain Barrier; Brain Neoplasms; Fluorine Radioisotopes; Humans; Medical Oncology; Microvessels; Radiopharmaceuticals; Tyrosine

Positron emission tomography (PET) imaging using amino acid tracers has in recent years become widely used in the diagnosis and prediction of disease course in diffuse low-grade gliomas (LGG). However, implications of preoperative PET for treatment and prognosis in this patient group have not been systematically studied. The aim of this systematic review was to evaluate the preoperative diagnostic and prognostic value of amino acid PET in suspected diffuse LGG. Medline, Cochrane Library, and Embase databases were systematically searched using keywords "PET," "low-grade glioma," and "amino acids tracers" with their respective synonyms. Out of 2137 eligible studies, 28 met the inclusion criteria. Increased amino acid uptake (lesion/brain) was consistently reported among included studies; in 25-92% of subsequently histopathology-verified LGG, in 83-100% of histopathology-verified HGG, and also in some non-neoplastic lesions. No consistent results were found in studies reporting hot spot areas on PET in MRI-suspected LGG. Thus, the diagnostic value of amino acid PET imaging in suspected LGG has proven difficult to interpret, showing clear overlap and inconsistencies among reported results. Similarly, the results regarding the prognostic value of PET in suspected LGG and the correlation between uptake ratios and the molecular tumor status of LGG were conflicting. This systematic review illustrates the difficulties with prognostic studies presenting data on group-level without adjustment for established clinical prognostic factors, leading to a loss of additional prognostic information. We conclude that the prognostic value of PET is limited to analysis of histological subgroups of LGG and is probably strongest when using kinetic analysis of dynamic FET uptake parameters.

Topics: Brain Neoplasms; Carbon Radioisotopes; Glioma; Humans; Methionine; Positron-Emission Tomography; Preoperative Period; Radiopharmaceuticals; Tyrosine

Routine diagnostics and treatment monitoring of brain tumors is usually based on contrast-enhanced MRI. However, the capacity of conventional MRI to differentiate tumor tissue from posttherapeutic effects following neurosurgical resection, chemoradiation, alkylating chemotherapy, radiosurgery, and/or immunotherapy may be limited. Metabolic imaging using PET can provide relevant additional information on tumor metabolism, which allows for more accurate diagnostics especially in clinically equivocal situations. This review article focuses predominantly on the amino acid PET tracers

Topics: Amino Acids; Brain Neoplasms; Dihydroxyphenylalanine; Humans; Methionine; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

Topics: Biopsy; Brain; Brain Neoplasms; Cell Proliferation; Diagnostic Imaging; Dihydroxyphenylalanine; Fluorodeoxyglucose F18; Humans; Lipids; Medical Oncology; Methionine; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a promising tracer for PET that has demonstrated convincing results especially in the diagnostics of brain tumors. In contrast to other radiolabeled amino acids, it can be produced with high efficiency and distributed in a satellite concept like the widely used 2-[18F]fluoro-2-deoxy-D-glucose. Although FET is not incorporated into proteins, it shows high uptake in cerebral gliomas and in extracranial squamous cell carcinomas owing to increased transport. The tracer exhibits high in vivo stability, low uptake in inflammatory tissue and suitable uptake kinetics for clinical imaging, which indicates that it may become a new standard tracer for PET. In this article, the present knowledge on the uptake mechanisms and the clinical applications of FET are reviewed and the clinical perspectives are discussed.

Topics: Animals; Biological Transport; Brain Neoplasms; Fluorine Radioisotopes; Humans; Positron-Emission Tomography; Tyrosine

The purpose of this prospective study was to clarify the value of FLT PET and FET PET for the noninvasive grading and prognosis of newly diagnosed gliomas.. Twenty patients with newly diagnosed gliomas were investigated with FLT and FET PET before surgery. FLT and FET uptakes were assessed by the maximum standardized uptake (SUVmax) of tumor, and the ratio to uptake in the normal brain parenchyma (TNR). All tumors were graded by WHO system.. FLT PET detected all 17 high-grade gliomas (HGG) and did not detect all 3 low-grade gliomas (LGG). FET PET detected all 20 HGG and LGG regardless of grading. The average FLT SUVmax in HGG and LGG was 1.51 ± 0.72 and 0.30 ± 0.07, and the average FLT TNR in HGG and LGG was 5.52 ± 3.09 and 1.12 ± 0.14, respectively. The differences of FLT SUVmax and TNR between HGG and LGG were statistically significant (p=0.0069, p=0.0070). The average FET SUVmax in HGG and LGG was 2.68 ± 0.86 and 1.36 ± 0.15, and the average FET TNR in HGG and LGG was 2.31 ± 0.73 and 1.27 ± 0.12, respectively. The differences of FET SUVmax and TNR between HGG and LGG were statistically significant (p=0.0129, p=0.0095).. FET PET has higher sensitivity in detection of gliomas rather than FLT PET, but it seems that FLT PET is better than FET PET for noninvasive grading and predicting prognosis of newly diagnosed gliomas, considering high contrast of FLT and overlap of FET uptakes between HGG and LGG.

Topics: Adult; Aged; Brain Neoplasms; Dideoxynucleosides; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Prognosis; Prospective Studies; Tyrosine

To assess the feasibility of synthesis of O-(2-[(18)F]-fluoroethyl)-l-tyrosine (FET), a new positron emission tomographic (PET) tracer described in several studies but not yet considered standard in management of glioma, in routine practice and to determine FET uptake in a homogeneous group of patients with suspected high-grade glioma.. Prospective nonrandomized trial.. Twelve patients with suspicion of high-grade glioma.. The mean (SD) FET uptake ratio was 3.15 (0.72) for the 12 patients and 3.16 (0.75) for the 11 patients with glioblastoma.. The initial results are promising and indicate that FET PET is a valuable and applicable tool for the imaging of high-grade glioma.

Topics: Brain; Brain Neoplasms; Glioblastoma; Humans; Image Interpretation, Computer-Assisted; Image Processing, Computer-Assisted; Positron-Emission Tomography; Prospective Studies; Tyrosine

Amino acid transport and protein synthesis are important steps of tumor growth. We investigated the time course of tumor metabolism in low-grade gliomas (LGG) during temozolomide chemotherapy, and compared metabolic responses as measured with positron emission tomography (PET) with volume responses as revealed by magnetic resonance imaging (MR). A homogeneous population of 11 patients with progressive non-enhancing LGG was prospectively studied. Imaging was done at 6-months intervals starting six months, and in a second series starting three months after treatment initiation. F-18 fluoro-ethyl-L-tyrosine (FET) uptake was quantified with PET as metabolically active tumor volume, and was compared with the tumor volume on MR. Response was defined as >or=10% reduction of the initial tumor volume. Eight patients showed metabolic responses. Already 3 months after start of chemotherapy the active FET volumes decreased in 2 patients to a mean of 44% from baseline. First MR volume responses were noted at 6 months. Responders showed a volume reduction to 31 +/- 23% (mean +/- SD) from baseline for FET, and to 73 +/- 26% for MR. The time to maximal volume reduction was 8.0 +/- 4.4 months for FET, and 15.0 +/- 3.0 months for MR. The initial metabolic response correlated with the best volume response on MR (Spearman Rank P = 0.011). Deactivation of amino acid transport represents an early indicator of chemotherapy response in LGG. Response assessment based on MR only has to be reconsidered. The time window obtained from PET may assist for individual treatment decisions in LGG patients.

Topics: Adult; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Female; Fluorine Radioisotopes; Follow-Up Studies; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Temozolomide; Time Factors; Tyrosine; Young Adult

The purpose of this study was to compare the diagnostic value of positron emission tomography (PET) using [(18)F]-fluorodeoxyglucose ((18)F-FDG) and O-(2-[(18)F]fluoroethyl)-l-tyrosine ((18)F-FET) in patients with brain lesions suspicious of cerebral gliomas.. Fifty-two patients with suspicion of cerebral glioma were included in this study. From 30 to 50 min after injection of 180 MBq (18)F-FET, a first PET scan ((18)F-FET scan) was performed. Thereafter, 240 MBq (18)F-FDG was injected and a second PET scan was acquired from 30 to 60 min after the second injection ((18)F-FET/(18)F-FDG scan). The cerebral accumulation of (18)F-FDG was calculated by decay corrected subtraction of the (18)F-FET scan from the (18)F-FET/(18)F-FDG scan. Tracer uptake was evaluated by visual scoring and by lesion-to-background (L/B) ratios. The imaging results were compared with the histological results and prognosis.. Histology revealed 24 low-grade gliomas (LGG) of World Health Organization (WHO) Grade II and 19 high-grade gliomas (HGG) of WHO Grade III or IV, as well as nine others, mainly benign histologies. The gliomas showed increased (18)F-FET uptake (>normal brain) in 86% and increased (18)F-FDG uptake (>white matter) in 35%. (18)F-FET PET provided diagnostically useful delineation of tumor extent while this was impractical with (18)F-FDG due to high tracer uptake in the gray matter. A local maximum in the tumor area for biopsy guidance could be identified with (18)F-FET in 76% and with (18)F-FDG in 28%. The L/B ratios showed significant differences between LGG and HGG for both tracers but considerable overlap so that reliable preoperative grading was not possible. A significant correlation of tracer uptake with overall survival was found with (18)F-FDG only. In some benign lesions like abscesses, increased uptake was observed for both tracers indicating a limited specificity of both techniques.. (18)F-FET PET is superior to (18)F-FDG for biopsy guidance and treatment planning of cerebral gliomas. The uptake of (18)F-FDG is associated with prognosis, but the predictive value is limited and a histological evaluation of tumor tissue remains necessary. Therefore, amino acids like (18)F-FET are the preferred PET tracers for the clinical management of cerebral gliomas.

Topics: Adolescent; Aged; Brain Neoplasms; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Male; Middle Aged; Positron-Emission Tomography; Prospective Studies; Tyrosine; Young Adult

Biological brain tumor imaging using O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET combined with inverse treatment planning for locally restricted dose escalation in patients with glioblastoma multiforme seems to be a promising approach.The aim of this study was to compare inverse with forward treatment planning for an integrated boost dose application in patients suffering from a glioblastoma multiforme, while biological target volumes are based on FET-PET and MRI data sets.. In 16 glioblastoma patients an intensity-modulated radiotherapy technique comprising an integrated boost (IB-IMRT) and a 3-dimensional conventional radiotherapy (3D-CRT) technique were generated for dosimetric comparison. FET-PET, MRI and treatment planning CT (P-CT) were co-registrated. The integrated boost volume (PTV1) was auto-contoured using a cut-off tumor-to-brain ratio (TBR) of > or = 1.6 from FET-PET. PTV2 delineation was MRI-based. The total dose was prescribed to 72 and 60 Gy for PTV1 and PTV2, using daily fractions of 2.4 and 2 Gy.. After auto-contouring of PTV1 a marked target shape complexity had an impact on the dosimetric outcome. Patients with 3-4 PTV1 subvolumes vs. a single volume revealed a significant decrease in mean dose (67.7 vs. 70.6 Gy). From convex to complex shaped PTV1 mean doses decreased from 71.3 Gy to 67.7 Gy. The homogeneity and conformity for PTV1 and PTV2 was significantly improved with IB-IMRT. With the use of IB-IMRT the minimum dose within PTV1 (61.1 vs. 57.4 Gy) and PTV2 (51.4 vs. 40.9 Gy) increased significantly, and the mean EUD for PTV2 was improved (59.9 vs. 55.3 Gy, p < 0.01). The EUD for PTV1 was only slightly improved (68.3 vs. 67.3 Gy). The EUD for the brain was equal with both planning techniques.. In the presented planning study the integrated boost concept based on inversely planned IB-IMRT is feasible. The FET-PET-based automatically contoured PTV1 can lead to very complex geometric configurations, limiting the achievable mean dose in the boost volume. With IB-IMRT a better homogeneity and conformity, compared to 3D-CRT, could be achieved.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Tyrosine

The aim of the present study was to evaluate whether extended analyses of O-(2-18F-fluoroethyl)-L-tyrosine (FET) uptake kinetics provide results superior to those of standard tumor-to-background ratios in predicting tumor grade in patients with pretreated gliomas.. Dynamic 18F-FET PET studies (0-40 min after injection of 180 MBq of 18F-FET) were performed on 45 glioma patients with suspected tumor recurrence after multimodal treatment. For the standard method, tumoral maximal standardized uptake value (SUVmax) and the ratio to the background were derived from a summed image 20-40 min after injection. Dynamic data evaluation comprised several approaches: first, SUV within a 90% isocontour threshold (SUV90) and the respective ratio to the background calculated for each time frame between 5 and 40 min after injection; second, the time to peak analysis; and third, various parameters accounting for the individual time course of 18F-FET uptake. Results were correlated with the histopathologic findings of MRI/PET-guided stereotactic biopsies and were evaluated with respect to their discriminatory power to separate low- from high-grade tumors using receiver-operating characteristic (ROC) analyses.. The parameters taking into account the individual time course of 18F-FET uptake were able to differentiate low-grade from high-grade recurrent astrocytomas with high diagnostic accuracy, reaching the best differentiation with a sensitivity and specificity of 92% and an area under the ROC curve (AUC) of 0.94. For the other parameters, the respective values were considerably lower (time to peak: 85% sensitivity and 88% specificity; SUV90-to-background ratio for single-frame evaluation of the early-uptake phase: 100% sensitivity, 62% specificity, and 0.81 AUC). The lowest performance was provided by the standard method (SUVmax: 73% sensitivity, 54% specificity, and 0.60 AUC; SUVmax-to-background ratio: 62% sensitivity, 62% specificity, and 0.59 AUC). Time-activity curves (5-40 min after injection) slightly and steadily increased in tumor-free patients and in low-grade tumors, whereas high-grade tumors showed an early peak around 10-15 min after injection followed by a decrease.. This study has shown differences in the dynamics of 18F-FET uptake between recurrent low- and high-grade gliomas. Therefore, parameters addressing the different kinetic behaviors allow discrimination with high diagnostic power between these 2 prognostically different groups. Thus, the techniques introduced here are clearly superior to the yet most widely used standard method.

Topics: Adult; Algorithms; Brain; Brain Neoplasms; Computer Simulation; Female; Glioma; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Tyrosine

Intracavitary radioimmunotherapy (RIT) offers an effective adjuvant therapeutic approach in patients with malignant gliomas. Since differentiation between recurrence and reactive changes following RIT has a critical impact on patient management, the aim of this study was to analyse the value of serial O-(2-[(18)F]fluoroethyl)-L: -tyrosine (FET) PET scans in monitoring the effects of this locoregional treatment.. Following conventional therapy, 24 glioma patients (5 WHO III, 19 WHO IV) underwent one to five RIT cycles with either (131)I-labelled (n=19) or (188)Re-labelled (n=5) anti-tenascin antibodies. Patients were monitored with serial FET PET scans (2-12 scans). For semiquantitative evaluation, maximal tumoural uptake (TU(max)) was evaluated and the ratio to background (BG) was calculated. Results of PET were correlated with histopathological findings (n=9) and long-term clinical follow-up for up to 87 months.. In seven tumour-free patients, PET revealed slightly increasing but homogeneous FET uptake surrounding the resection cavity with a peak up to 18 months following RIT (TU(max)/BG 2.07+/-0.25) but stable or decreasing values during further follow-up (last follow-up: TU(max)/BG 1.63+/-0.22). Seventeen patients developed regrowth of residual tumour/tumour recurrence showing additional nodular FET uptake (TU(max)/BG 2.79+/-0.53). A threshold value of 2.4 (TU(max)/BG) allowed best differentiation between recurrence and reactive changes (sensitivity 82%, specificity 100%).. FET PET is a sensitive tool for monitoring the effects of locoregional RIT. Homogeneous, slightly increasing FET uptake around the tumour cavity with a peak up to 18 months after RIT, followed by stable or decreasing uptake, points to benign, therapy-related changes. In contrast, nodular uptake is a reliable indicator of recurrence.

Topics: Adult; Brachytherapy; Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Radioimmunotherapy; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Tyrosine

Thermotherapy using magnetic nanoparticles (nano cancer therapy) is a new concept of local tumour therapy, which is based on controlled heating of intra-tumoural injected magnetic nanoparticles. The aim of this study was to evaluate the usefulness of PET with a recently introduced amino acid tracer O-(2-[18F]fluoroethyl)-]L-tyrosine (FET) for targeting the nanoparticles implantation.. Eleven patients with glioblastoma recurrences underwent MR and FET-PET imaging for planning of the nano cancer therapy. Thereafter, the gross tumour volumes (GTV) were defined, taking into consideration the results of both imaging tools.. The MRI-based mean GTV was 24.3 cm3 (range 2.5-59.7) and the PET-based mean GTV 31.9 cm3 (range 5.2-77.9). On the average the MRI identified an additional 8.9 +/- 4.7 cm3 and the FET-PET scan-an additional 16.5 +/- 15.2 cm3 outside of the common GTV (15.4 +/- 11.0 cm3). The mean final GTV accounted to 33.8 cm3 (range, 5.2-77.9). The additional information of FET-PET led to an increase in GTV by 22-286% in eight patients and to a decrease of 23% and 26%, respectively, in two patients. In one patient, the final GTV was defined on the basis of MRI data only.. FET-PET adds important information on the actual tumour volume in recurrent glioblastomas and is highly valuable for defining the target volume for the nano cancer therapy.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioblastoma; Humans; Hyperthermia, Induced; Magnetic Resonance Imaging; Magnetics; Male; Middle Aged; Nanostructures; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiotherapy Planning, Computer-Assisted; Tyrosine

The aim of this study was to evaluate the differential uptake of O-(2-[18F]fluorethyl)-L-tyrosine (FET) in suspected primary brain tumours.. Positron emission tomography (PET) was performed in 44 patients referred for the evaluation of a suspected brain tumour. Acquisition consisted of four 10-min frames starting upon i.v. injection of FET. Tumour uptake was calculated as the ratio of maximal tumour intensity to mean activity within a reference region (FETmax).. FET uptake above the cortical level was observed in 35/44 lesions. All histologically confirmed gliomas and many other lesions showed FET uptake to a variable extent. No uptake was observed in nine lesions (one inflammatory lesion, one dysembryoplastic neuroepithelial tumour, one mature teratoma, six lesions without histological confirmation). An analysis of uptake dynamics was done in the patients with increased FET uptake (22 gliomas, three lymphomas, three non-neoplastic lesions, three lesions with unknown histology and four other primaries). Upon classification of tumours into low (i.e. WHO I and II) and high grade (i.e. WHO III and IV), a significant difference in FETmax between the two categories was observed only in the first image frame (0-10 min p.i.), with FETmax=2.0 in low-grade and 3.2 in high-grade tumours (p<0.05); no significant differences were found in frame 4 (30-40 min p.i.), with FETmax=2.4 vs 2.7. Similar results were obtained when the analysis was applied only to astrocytic tumours (2.0 vs 3.1 in the first frame; 2.4 vs 2.6 in the fourth frame).. These initial results indicate that FET PET is a useful method to identify malignant brain lesions. It appears that high- and low-grade brain tumours exhibit a different uptake kinetics of FET. A kinetic analysis of FET PET may provide additional information in the differentiation of suspected brain lesions.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Child; Child, Preschool; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

Convection-enhanced delivery (CED) of paclitaxel is a new locoregional approach for patients with recurrent glioblastoma. The aim of this study was to evaluate O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) in monitoring the effects of this type of direct drug delivery.. Eight patients with recurrent glioblastoma underwent CED of paclitaxel, which was infused over stereotactically placed catheters into the tumour. FET PET and MRI were performed before and 4 weeks after therapy and then at 3-month intervals to document follow-up. For quantitative evaluation, SUV(max)(tumour)/SUV(mean)(background) ratios were calculated.. At baseline all tumours showed gadolinium enhancement and high FET uptake (SUV(max)/BG 3.2+/-0.8). Four weeks after CED, a statistically significant decrease in FET uptake was seen (SUV(max)/BG-17%; p<0.01). During follow-up, no recurrence was observed within the CED area. Two out of eight patients with extended tumours died 4 and 5 months after treatment, most probably from local complications. Temporarily stable disease with stable FET uptake was observed in six of eight patients; this was followed by progression and increasing FET uptake ratios (+46%) distant from the CED area in five of the six patients 3-13 months after CED. One patient still presents stable FET uptake 10 months after CED. MRI showed unchanged/increasing contrast enhancement and oedema without ability to reliably assess disease progression.. FET PET is a valuable tool in monitoring the effects of CED of paclitaxel. In long-term follow-up, stable or decreasing FET uptake, even in contrast-enhancing lesions, is suggestive of reactive changes, whereas increasing ratios appear always to be indicative of recurrence. Therefore, FET PET is more reliable than MRI in differentiating stable disease from tumour regrowth.

Topics: Antineoplastic Agents; Brain Neoplasms; Convection; Drug Delivery Systems; Female; Glioblastoma; Humans; Infusions, Intralesional; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Tyrosine

The aim of this study was to compare PET with O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) and SPECT with 3-(123)I-iodo-alpha-methyl- L-tyrosine ((123)I-IMT) in patients with brain tumors.. Twenty patients with a suspected brain tumor were investigated by (18)F-FET PET, (123)I-IMT SPECT, and MRI within 3 wk. Region-of-interest analyses were performed on coregistered PET/SPECT/MRI images and the tumor-to-brain ratio (TBR), muscle-to-brain ratio (MBR), cerebellum-to-brain ratio (CerBR), and sinus-to-brain ratio (SBR) were calculated. In addition, the presence of tumor and the discrimination of anatomic structures on (18)F-FET PET and (123)I-IMT SPECT images were visually determined by 3 observers who were unaware of clinical data.. The TBR of (18)F-FET and (123)I-IMT uptake in cerebral tumors showed a highly significant correlation (r = 0.96; P < 0.001). In the visual analysis for the presence or absence of tumors, no differences for (123)I-IMT SPECT and (18)F-FET PET were found in 19 of 20 patients; in one patient a low-grade glioma was only identified on (18)F-FET PET images but not on (123)I-IMT SPECT images. The contrast between tumor and normal brain was significantly higher in (18)F-FET PET (TBR, 2.0 +/- 0.9) than in (123)I-IMT SPECT (TBR, 1.5 +/- 0.5). The discrimination of anatomic structures yielded a significantly better score on (18)F-FET PET images (rating score, 2.6 +/- 0.9) compared with (123)I-IMT SPECT images (rating score, 1.7 +/- 0.9). The uptake of (18)F-FET in the muscles was significantly higher compared with (123)I-IMT (MBR (18)F-FET, 1.4 +/- 0.3; MBR (123)I-IMT, 0.6 +/- 0.2; P < 0.001) and (18)F-FET demonstrated a significantly higher blood-pool radioactivity than (123)I-IMT (SBR (18)F-FET, 1.3 +/- 0.2; SBR (123)I-IMT, 0.8 +/- 0.2; P < 0.001).. The significant correlation of the TBRs of (18)F-FET and (123)I-IMT indicates that clinical experiences of brain tumor diagnostics with (123)I-IMT SPECT might be valid for (18)F-FET PET although substantial differences of the physiologic behavior were identified in extracerebral tissue. As (18)F-FET PET allows improved discrimination of anatomic structures and the tumor-to-brain contrast was significantly superior compared with (123)I-IMT SPECT scans, the results are encouraging for further evaluation of (18)F-FET for imaging brain tumors.

Topics: Adult; Aged; Brain Neoplasms; Female; Fluorine Radioisotopes; Humans; Magnetic Resonance Imaging; Male; Methyltyrosines; Middle Aged; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Subtraction Technique; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon; Tyrosine

The prognosis of patients with recurrent gliomas depends on reliable and early diagnosis of tumour recurrence after initial therapy. In this context, magnetic resonance imaging (MRI) and computed tomography (CT) often fail to differentiate between radiation- and tumour-induced contrast enhancement. Furthermore, absence of contrast enhancement, or even of 18F-fluorodeoxyglucose uptake in PET, does not exclude recurrence. The aim of this study was to establish the diagnostic value of O-(2-[18F]fluoroethyl)- L-tyrosine (FET) PET in recurrent gliomas.. Fifty-three patients with glioma (primary grading: 27=WHO grade IV, 16=grade III, 9=grade II, 1=grade I) and clinically suspected recurrence underwent FET PET scans 4-180 months after different treatment modalities. For semiquantitative evaluation, maximal SUV (SUVmax) and mean SUV within 80% and 70% isocontour thresholds (SUV80/SUV70) were evaluated and the respective ratios to the background (BG) were calculated. PET results were correlated with MRI/CT, clinical follow-up or biopsy findings.. All patients presented with FET uptake, of varying intensity, in the area of the primary tumour after initial therapy. In the 42 patients with confirmed recurrence, there was additional distinct focal FET uptake with significantly higher values compared with those in the 11 patients without clinical signs of recurrence and showing only low and homogeneous FET uptake at the margins of the resection cavity. With respect to tumour grading, there was a slight but non-significant increase from WHO II (SUVmax/BG: 2.53+/-0.28) to WHO III (SUVmax/BG: 2.84+/-0.49) and WHO IV (SUVmax/BG: 3.55+/-1.07) recurrence.. FET PET reliably distinguishes between post-therapeutic benign lesions and tumour recurrence after initial treatment of low- and high-grade gliomas.

Topics: Brain Neoplasms; Fluorine Radioisotopes; Glioma; Humans; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Tyrosine

O-(2-[18F]Fluoroethyl)-L-tyrosine (FET) is a recently described amino acid analogue that has shown high accumulation in animal tumours. The aim of this study was to compare the uptake of FET with that of L-[methyl-11C]methionine (MET) in patients with suspected primary or recurrent intracerebral tumours. Sixteen consecutive patients with intracerebral lesions were studied on the same day by positron emission tomography (PET) using MET and FET. Uptake of FET and MET was quantified by standardized uptake values. Tracer kinetics for normal brain and intracerebral lesions were compared. On the basis of the MET-PET studies, viable tumour tissue was found in 13 patients. All tumours showed rapid uptake of FET and were visualized with high contrast. Mean uptake of FET for normal grey matter, white matter and tumour tissue was 1.1+/-0.2, 0.8+/-0.2 and 2.7+/-0.8 SUV, respectively. In all three tissues, uptake of MET was slightly higher (1.4+/-0.2, 0.9+/-0.1 and 3.3+/-1.0 SUV; P<0.01). However, contrast between tumour and normal tissues was not significantly different between MET and FET. Uptake of FET in non-neoplastic lesions (1.0+/-0.1 SUV) was significantly lower than in tumour tissue (P = 0.007). For all lesions there was a close correlation (r = 0.98) between MET and FET uptake. In conclusion, in PET studies of human brain tumours, the uptake and image contrast of FET appear to be very similar to those of MET. The specificity of FET for tumour tissue is promising but has to be addressed in a larger series of patients with non-neoplastic lesions.

Topics: Adult; Aged; Brain Neoplasms; Female; Fluorine Radioisotopes; Humans; Image Interpretation, Computer-Assisted; Image Processing, Computer-Assisted; Male; Methionine; Middle Aged; Radiopharmaceuticals; Tomography, Emission-Computed; Tyrosine

The CeTeG/NOA-09 phase III trial demonstrated a significant survival benefit of lomustine-temozolomide chemoradiation in patients with newly diagnosed glioblastoma with methylated O. We retrospectively identified patients (i) who were treated off-study according to the CeTeG/NOA-09 protocol, (ii) had equivocal MRI findings after radiotherapy, and (iii) underwent additional FET-PET imaging for diagnostic evaluation (number of scans, 1-3). Maximum and mean tumor-to-brain ratios (TBR. We identified 23 patients with 32 FET-PET scans. Within 5-25 weeks after radiotherapy (median time, 9 weeks), pseudoprogression occurred in 11 patients (48%). The parameter TBR. The data suggest that FET-PET parameters are of significant clinical value to diagnose pseudoprogression related to lomustine-temozolomide chemoradiation.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chemoradiotherapy; Disease Progression; Female; Glioblastoma; Humans; Lomustine; Male; Middle Aged; Positron-Emission Tomography; Retrospective Studies; Temozolomide; Tyrosine

PET using

Topics: Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Preoperative Period; Tyrosine

Positron emission tomography (PET) using O-(2-[. Ten patients with untreated cerebral gliomas and one patient with a recurrent glioblastoma (GBM) were investigated by dynamic [. NaT (p = 0.05), tumor-to-brain ratios (TBR) of NaT (p = 0.02), NaNR (p = 0.003), and the ratio of NaT/NaR (p < 0.001) were significantly higher in IDH-mutated than in IDH-wild-type gliomas (n = 5 patients each) while NaR was significantly lower in IDH-mutated gliomas (p = 0.01). [. Sodium MRI appears to be more strongly related to the IDH mutational status than are [

Topics: Adult; Brain Neoplasms; Cohort Studies; Female; Fluorine Radioisotopes; Glioma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Middle Aged; Pilot Projects; Positron-Emission Tomography; Radiopharmaceuticals; Tumor Burden; Tyrosine

Quantitative parametric images of O-(2-[

Topics: Adult; Aged; Brain Mapping; Brain Neoplasms; Fluorine Radioisotopes; Glioma; Humans; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Tissue Distribution; Tyrosine; Young Adult

Topics: Adult; Aged; Brain Neoplasms; Diagnosis, Differential; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Retrospective Studies; Tyrosine; Young Adult

GTV definition for re-irradiation treatment planning in recurrent glioblastoma (rGBM) is usually based on contrast-enhanced MRI (GdT1w-MRI) and, for an increased specificity, on amino acid PET. Diffusion-weighted (DWI) MRI and ADC maps can reveal regions of high cellularity as surrogate for active tumor. The objective of this study was to compare the localization and quality of diffusion restriction foci (GTV-ADClow) with FET-PET (GTV-PET) and GdT1w-MRI (GTV-GdT1w-MRI).. We prospectively evaluated 41 patients, who received a fractionated stereotactic re-irradiation for rGBM. GTV-PET was generated automatically (tumor-to-background ratio 1.7-1.8) and manually customized. GTV-ADClow was manually defined based on DWI data (3D diffusion gradients, b = 0, 1000 s/mm. Unexpectedly, GTV-ADClow overlapped only partially with FET-PET and GdT1w-MRI in rGBM. Moreover, GTV-ADClow correlated poorly with later rGBM-recurrences. Seeing as a restricted diffusion is known to correlate with hypercellularity, this imaging discrepancy could only be further explained in histopathological studies.

Topics: Adult; Aged; Brain Neoplasms; Diffusion Magnetic Resonance Imaging; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Prospective Studies; Radiosurgery; Re-Irradiation; Tumor Burden; Tyrosine

Glioblastoma inevitably recurs despite aggressive therapy. Therefore, it would be helpful to predict the location of tumor recurrence from postoperative imaging to customize further treatment. O-(2-. Thirty-two consecutive patients with perioperative and follow-up imaging data available were included. On postoperative FET-PET, the tumor/normal brain (TTB) ratio around the resection cavity borders was measured. Increased TTB ratios were recorded and anatomically correlated with the site of later tumor recurrence. On postoperative magnetic resonance imaging (MRI), residual contrast-enhancing tumor correlated with the site of later tumor recurrence.. Location of progression was predictable using MRI alone in 42% of patients by residual tumor on postoperative MRI. FET-PET was predictive in 25 patients by a clear hot spot at the site of later tumor recurrence. In 3 patients, it was partially predictive and in 4 was not predictive of the tumor recurrence location. One patient without any tracer uptake was recurrence free at the last follow-up examination. In contrast to the postoperative MRI results, tumor recurrence was found in 79% at a site of elevated TTB ratio on postoperative FET-PET. Therefore, the predictability of the tumor recurrence location using postoperative FET-PET was greater than that with MRI, and all cases predictable using MRI could have been predicted using FET-PET.. Postoperative FET-PET can be helpful for planning subsequent therapy, such as repeat resection or radiotherapy, because tumor recurrence can be predicted with relatively greater sensitivity than with MRI alone.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Electroencephalography; Evoked Potentials, Somatosensory; Female; Follow-Up Studies; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Predictive Value of Tests; Retrospective Studies; Tomography Scanners, X-Ray Computed; Tyrosine

We sought to assess the influence of the clinical introduction of new radiotherapy technologies on glioblastoma patients' outcomes.. Newly diagnosed glioblastoma patients treated with 60 Gy and temozolomide (2005-2014) were analyzed. The patients' GTV and CTV were defined based on MR (n = 521) or FET-PET/MR (n = 190), and were treated using conformal radiotherapy (CRT, n = 159) or image-guided volumetric modulated arc therapy with hippocampal sparing (IG-VMAT, n = 362). Progression-free survival (PFS) was assessed using the McDonald criteria. Associations between clinical data, dosimetry data, treatment technology, for PFS and overall survival (OS) were explored.. The PFS (7 months) and OS (15 months) were unaffected by CRT, IG-VMAT and FET-PET technology. Mean brain dose was correlated with tumor volume, and was lower for IG-VMAT vs. CRT (p < 0.001). Larger mean brain dose was associated with inferior PFS (univariate/multivariate Cox models, p < 0.001) and OS (univariate, p < 0.001). Multivariate Cox models revealed association of larger mean brainstem dose (p < 0.001), BTV (p = 0.045), steroid use at baseline (p = 0.003), age (p = 0.019) and MGMT status (p = 0.022) with lower OS.. Introduction of hippocampal-sparing IG-VMAT technology appeared to be safe, and may have reduced toxicity and cognitive impairment. Larger mean brain dose was strongly associated with inferior PFS and OS.

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Middle Aged; Positron-Emission Tomography; Proportional Hazards Models; Radiotherapy, Intensity-Modulated; Treatment Outcome; Tumor Burden; Tyrosine

PET/CT using O-(2-[F]fluoroethyl)-L-tyrosine (F-FET) has proven valuable in differentiating tumor recurrence and progression from therapy-induced changes. This study aimed to investigate the diagnostic performance of several analytic approaches in the setting of suspected late pseudoprogression (PsP) in glioblastoma multiforme (GBM).. Retrospective analysis of tumor recurrence was performed in 36 patients with histopathologically confirmed GBM and suspicion of recurrence/disease progression more than 12 weeks from cessation of irradiation based on MRI and Response Assessment in Neuro-Oncology working group criteria. For differentiation of late PsP from true tumor recurrence, images were analyzed semiquantitatively employing tumor-to-brain ratios using 5 different approaches for tumor and normal brain reference region definition, respectively. Histopathology and/or clinical and imaging follow-up served as reference. Respective areas under the receiver operating characteristic curve were compared.. F-FET PET was able to reliably differentiate PsP from true tumor progression with areas under the receiver operating characteristic curve ranging from 0.80 to 0.88 (all P < 0.01). Irrespective of the approach chosen, the classification differences between the applied methods were not significant (all P > 0.05), albeit approaches focusing on voxels with the highest uptake tended to perform superior.. Irrespective of the analytical approach, F-FET PET is a robust tool for detection of late PsP with only minor differences between different analytical approaches. However, methodological standardization and harmonization are needed to ensure comparability between different centers.

Topics: Adult; Aged; Brain Neoplasms; Disease Progression; Female; Glioblastoma; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Retrospective Studies; ROC Curve; Tyrosine; Young Adult

A variety of neoplastic and nonneoplastic conditions involve the corpus callosum, which may result in a "butterfly" appearance on conventional MRI. Typically, that pattern shows a bilateral and heterogeneous contrast enhancement of the lesion, occasionally with central nonenhancing areas indicating intralesional necrosis. In contrast, anaplastic gliomas may show only minimal or even a lack of contrast enhancement on MRI. We here report neuroimaging findings in a 69-year-old man with a "butterfly" pattern on dynamic FET [O-(2-[F]-fluoroethyl)-L-tyrosine] PET and the diagnosis of an anaplastic astrocytoma (WHO grade III; IDH-1/-2 wildtype, no 1p/19q co-deletion) but without typical MRI contrast enhancement.

Topics: Aged; Astrocytoma; Brain Neoplasms; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Tyrosine

PET using the amino-acid O-(2-

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; Brain; Brain Neoplasms; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Reference Standards; Retrospective Studies; Sex Factors; Tyrosine; Young Adult

Amino acid positron emission tomography (PET) using O-(2-[. A 61-year-old patient with glioblastoma initially underwent partial tumor resection and died 11 weeks after completion of chemoradiation with concurrent temozolomide. Three days before the patient died, a follow-up FET PET and MRI scan indicated tumor progression. Autopsy was performed 48 hours after death. After formalin fixation, a 7-cm bihemispherical segment of the brain containing the entire tumor mass was cut into 3500 consecutive 20μm coronal sections. Representative sections were stained with hematoxylin and eosin stain, cresyl violet, and glial fibrillary acidic protein immunohistochemistry. An experienced neuropathologist identified areas of dense and diffuse neoplastic infiltration, astrogliosis, and necrosis. In vivo FET PET, MRI datasets, and postmortem histology were co-registered and compared by 3 experienced physicians.. Increased uptake of FET in the area of equivocal contrast enhancement on MRI correlated very well with dense infiltration by vital tumor cells and showed tracer kinetics typical for malignant gliomas. An area of predominantly reactive astrogliosis showed only moderate uptake of FET and tracer kinetics usually observed in benign lesions.. This case report impressively documents the correct imaging of a progressive glioblastoma by FET PET.

Topics: Brain; Brain Neoplasms; Combined Modality Therapy; Fatal Outcome; Glioblastoma; Humans; Magnetic Resonance Imaging; Middle Aged; Neuroimaging; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

The aim of this study was to analyze the robustness and diagnostic value of different compartment models for dynamic

Topics: Aged; Antineoplastic Agents; Brain Neoplasms; Carbon; Female; Glioma; Heavy Ion Radiotherapy; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Models, Statistical; Neoplasm Grading; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Survival Analysis; Temozolomide; Tyrosine

The aim of this study was to investigate the potential of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for differentiating local recurrent brain metastasis from radiation injury after radiotherapy since contrast-enhanced MRI often remains inconclusive.. Sixty-two patients (mean age, 55 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 76) on MRI after radiotherapy of brain metastases (predominantly stereotactic radiosurgery) were investigated with dynamic 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) of 18F-FET uptake were determined (20-40 min postinjection) as well as tracer uptake kinetics (ie, time-to-peak and slope of time-activity curves). Diagnoses were confirmed histologically (34%; 26 lesions in 25 patients) or by clinical follow-up (66%; 50 lesions in 37 patients). Diagnostic accuracies of PET parameters for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or the chi-square test.. TBRs were significantly higher in recurrent metastases (n = 36) than in radiation injuries (n = 40) (TBRmax 3.3 ± 1.0 vs 2.2 ± 0.4, P < .001; TBRmean 2.2 ± 0.4 vs 1.7 ± 0.3, P < .001). The highest accuracy (88%) for diagnosing local recurrent metastasis could be obtained with TBRs in combination with the slope of time-activity curves (P < .001).. The results of this study confirm previous preliminary observations that the combined evaluation of the TBRs of 18F-FET uptake and the slope of time-activity curves can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. 18F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Diagnosis, Differential; Disease Progression; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Positron-Emission Tomography; Prognosis; Radiation Injuries; Radiopharmaceuticals; Radiotherapy; Tyrosine; Young Adult

Glioblastoma patients show a great variability in progression free survival (PFS) and overall survival (OS). To gain additional pretherapeutic information, we explored the potential of O-(2-. We retrospectively analyzed 146 consecutively treated, newly diagnosed glioblastoma patients. All patients were treated with temozolomide and radiation therapy (RT). CT/MR and FET PET scans were obtained postoperatively for RT planning. We used Cox proportional hazards models with OS and PFS as endpoints, to test the prognostic value of FET PET biological tumor volume (BTV).. Median follow-up time was 14 months, and median OS and PFS were 16.5 and 6.5 months, respectively. In the multivariate analysis, increasing BTV (HR = 1.17, P < 0.001), poor performance status (HR = 2.35, P < 0.001), O(6)-methylguanine-DNA methyltransferase protein status (HR = 1.61, P = 0.024) and higher age (HR = 1.32, P = 0.013) were independent prognostic factors of poor OS. For poor PFS, only increasing BTV (HR = 1.18; P = 0.002) was prognostic. A prognostic index for OS was created based on the identified prognostic factors.. Large BTV on FET PET is an independent prognostic factor of poor OS and PFS in glioblastoma patients. With the introduction of FET PET, we obtain a prognostic index that can help in glioblastoma treatment planning.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Tomography, X-Ray Computed; Tyrosine

O-(2-fluoroethyl)-L-tyrosine (FET) PET/CT is a promising imaging modality for brain tumor imaging because of its reported high sensitivity for biologically active tumor tissue. We present a case of biopsy-proven neurosarcoidosis showing FET uptake. It is an important cause of false-positive uptake on FET PET/CT.

Topics: Adult; Brain Neoplasms; Central Nervous System Diseases; False Positive Reactions; Fluorodeoxyglucose F18; Humans; Male; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sarcoidosis; Tyrosine

Most high-grade gliomas (HGG) recur after initial multimodal therapy and re-irradiation (Re-RT) has been shown to be a valuable re-treatment option in selected patients. We evaluated the prognostic value of dynamic time-to-peak analysis and early static summation images in O-(2-

Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Immunological; Bevacizumab; Brain Neoplasms; Female; Glioma; Humans; Karnofsky Performance Status; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Nonlinear Dynamics; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Re-Irradiation; Survival Analysis; Time Factors; Tyrosine; Young Adult

To evaluate the patterns of failure following clinical introduction of amino-acid O-(2-[. The first 66 consecutive patients with confirmed histology, scanned using FET-PET/CT and MRI were selected for evaluation. Chemo-radiotherapy was delivered to a volume based on both MRI and FET-PET (PET. Fifty patients were evaluable, with median follow-up of 45months. Central, in-field, marginal and distant recurrences were observed for 82%, 10%, 2%, and 6% of the patients, respectively. We found a volumetric overlap of 26%, 31% and 39% of the RV with the contrast-enhancing MR volume, PET. The combined MRPET

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Disease Progression; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiology, Interventional; Radiopharmaceuticals; Radiotherapy, Image-Guided; Retrospective Studies; Treatment Failure; Tyrosine

Positron emission tomography (PET) using O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of (18)F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy.. F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10-11 days of tumor growth, the animals underwent dynamic PET after injection of (18)F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of (18)F-FET uptake (18-61 min p.i.) and the slope of the time-activity-curves (TAC) (18-61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC).. The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (-8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC.. TBR of (18)F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation.

Topics: Animals; Biological Transport; Brain Neoplasms; Dexamethasone; Disease Models, Animal; Glioma; Kinetics; Male; Positron-Emission Tomography; Rats; Reproducibility of Results; Tyrosine

Pseudoprogression (PsP) is characterized by therapy-associated but not tumor growth-associated increases of contrast-enhancing glioblastoma lesions on MRI. Although typically occurring during the first 3 months after radiochemotherapy, PsP may occur later in the course of the disease and may then be particularly difficult to distinguish from true tumor progression. We explored PET using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET-PET) to approach the diagnostic dilemma.. Twenty-six patients with glioblastoma that presented with increasing contrast-enhancing lesions later than 3 months after completion of radiochemotherapy underwent (18)F-FET-PET. Maximum and mean tumor/brain ratios (TBRmax and TBRmean) of (18)F-FET uptake as well as time-to-peak (TTP) and patterns of the time-activity curves were determined. The final diagnosis of true progression versus late PsP was based on follow-up MRI using RANO criteria.. Late PsP occurred in 7 patients with a median time from radiochemotherapy completion of 24 weeks while the remaining patients showed true tumor progression. TBRmax and TBRmean were significantly higher in patients with true progression than in patients with late PsP (TBRmax 2.4 ± 0.1 vs. 1.5 ± 0.2, P = 0.003; TBRmean 2.1 ± 0.1 vs. 1.5 ± 0.2, P = 0.012) whereas TTP was significantly shorter (mean TTP 25 ± 2 vs. 40 ± 2 min, P < 0.001). ROC analysis yielded an optimal cutoff value of 1.9 for TBRmax to differentiate between true progression and late PsP (sensitivity 84%, specificity 86%, accuracy 85%, P = 0.015).. O-(2-[(18)F]fluoroethyl)-L-tyrosine PET provides valuable information in assessing the elusive phenomenon of late PsP. Clin Cancer Res; 22(9); 2190-6. ©2015 AACR.

Topics: Adult; Aged; Brain Neoplasms; Chemoradiotherapy; Disease Progression; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity; Tyrosine; Young Adult

O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography ((18)F-FET-PET) imaging is applied for tumor grading, prognostic stratification, and diagnosis of tumor recurrence, especially in high-grade gliomas. Experience with (18)F-FET-PET imaging in low-grade gliomas is limited. Therefore, the objective of the present study was to assess (18)F-FET-PET tracer uptake in low-grade gliomas and to investigate possible correlations with contrast enhancement in magnetic resonance imaging (MRI) and histopathology.. A total of 65 patients (29 female, 36 male, median age 38 years) with newly diagnosed or recurrent low-grade gliomas for whom preoperative MRI and (18)F-FET-PET imaging were available were included. Tumor entity, tumor location, as well as histopathology (isocitrate dehydrogenase [IDH] 1/2 mutation, Ki67, p53, oligodendroglial differentiation, 1p19q codeletion), and progression-free survival were assessed. (18)F-FET-PET images were acquired and fused to MRI (T2-weighted fluid-attenuated inversion recovery) and tumor volume was measured in areas with a tumor-to-background ratio >1.3, >1.6, and >2.0 and in MRI.. PET tracer uptake was observed in 78.5% of all World Health Organization Grade I and II tumors. (18)F-FET uptake showed a high negative predictive value for oligodendroglial components and for 1p19q codeletion. No further significant correlation between histologic features, progression-free survival, or IDH1/2 mutation status and tracer uptake was observed.. We found that 78.5% of low-grade gliomas do show elevated tracer uptake in (18)F-FET-PET imaging. Low-grade glioma without tracer uptake exclude oligodendroglial differentiation and 1p19q codeletion. Further differentiation between molecular subtypes is not possible with static (18)F-FET-PET. No correlation of progression-free survival to tracer uptake and IDH1/2-mutation status was observed.

Topics: Adult; Biomarkers, Tumor; Brain; Brain Neoplasms; Disease-Free Survival; Female; Glioma; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity; Tumor Burden; Tyrosine

After focused high dose radiotherapy of brain metastases, differentiation between tumor recurrence and radiation-induced lesions by conventional MRI is challenging. This study investigates the usefulness of dynamic O-(2-. Twenty-two patients with 34 brain metastases (median age 61.9 years) were included. Due to follow-up scan evaluations after repeated treatment in a subset of patients, a total of 50 lesions with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy could be evaluated.. Tumor recurrence was found in 21/50 cases (15/21 verified by histology, 6/21 by radiological-clinical follow-up) and radiation-induced changes in 29/50 cases (5/29 verified by histology, 24/29 by radiological-clinical follow-up). Median clinical-radiological follow-up was 28.3 months (range 4.2-99.1 months).. In patients with MRI-suspected tumor recurrence after focused high dose radiotherapy,

Topics: Brachytherapy; Brain Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiosurgery; ROC Curve; Tyrosine

MRI alone has its limitations for target selection in biopsy or resection in newly diagnosed and pretreated pediatric brain tumor patients. (18)F-FET-PET imaging is considered to identify metabolically active tumor tissue and to differentiate it from therapy-associated changes. We retrospectively analyzed our experience with (18)F-FET-PET in targeted surgical interventions for pediatric brain tumors.. In 26 cases with lesions suspicious of a growing brain tumor on MRI, either newly diagnosed or after antitumoral treatment led to (18)F-FET-PET imaging for target selection prior to stereotactic biopsy, navigated open biopsy or navigated microsurgical tumor resection. Indications for (18)F-FET-PET imaging were visualization of metabolic active tumor tissue within diffuse tumors or pretreated lesions as well as depicting their extent.. (18)F-FET-PET integration in surgery was feasible in all patients using stereotaxy or neuronavigation. Sensitivity for tumor detection was 20/24. (18)F-FET-PET was false positive in two pretreated patients.. (18)F-FET-PET imaging is helpful for target selection and can be integrated in surgical guidance. (18)F-FET-PET image-guided surgical targeting yielded histological diagnosis with decent specificity and high sensitivity in our cohort of pediatric brain tumor patients. Our results warrant further evaluation of (18)F-FET-PET imaging for surgical guidance.

Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Infant; Male; Neuronavigation; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Tyrosine

The follow-up of glioblastoma patients after radiochemotherapy with conventional MRI can be difficult since reactive alterations to the blood-brain barrier with contrast enhancement may mimic tumour progression (i.e. pseudoprogression, PsP). The aim of this study was to assess the clinical value of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET in the differentiation of PsP and early tumour progression (EP) after radiochemotherapy of glioblastoma.. A group of 22 glioblastoma patients with new contrast-enhancing lesions or lesions showing increased enhancement (>25 %) on standard MRI within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median 7 weeks) were additionally examined using amino acid PET with (18)F-FET. Maximum and mean tumour-to-brain ratios (TBRmax, TBRmean) were determined. (18)F-FET uptake kinetic parameters (i.e. patterns of time-activity curves, TAC) were also evaluated. Classification as PsP or EP was based on the clinical course (no treatment change at least for 6 months), follow-up MR imaging and/or histopathological findings. Imaging results were also related to overall survival (OS).. PsP was confirmed in 11 of the 22 patients. In patients with PsP, (18)F-FET uptake was significantly lower than in patients with EP (TBRmax 1.9 ± 0.4 vs. 2.8 ± 0.5, TBRmean 1.8 ± 0.2 vs. 2.3 ± 0.3; both P < 0.001) and presence of MGMT promoter methylation was significantly more frequent (P = 0.05). Furthermore, a TAC type II or III was more frequently present in patients with EP (P = 0.04). Receiver operating characteristic analysis showed that the optimal (18)F-FET TBRmax cut-off value for identifying PsP was 2.3 (sensitivity 100 %, specificity 91 %, accuracy 96 %, AUC 0.94 ± 0.06; P < 0.001). Univariate survival analysis showed that a TBRmax <2.3 predicted a significantly longer OS (median OS 23 vs. 12 months; P = 0.046).. (18)F-FET PET may facilitate the diagnosis of PsP following radiochemotherapy of glioblastoma.

Topics: Adult; Aged; Brain Neoplasms; Disease Progression; False Positive Reactions; Female; Glioblastoma; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

Experience regarding O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET in children and adolescents with brain tumors is limited.. Sixty-nine (18)F-FET PET scans of 48 children and adolescents (median age, 13 y; range, 1-18 y) were analyzed retrospectively. Twenty-six scans to assess newly diagnosed cerebral lesions, 24 scans for diagnosing tumor progression or recurrence, 8 scans for monitoring of chemotherapy effects, and 11 scans for the detection of residual tumor after resection were obtained. Maximum and mean tumor-to-brain ratios (TBRs) were determined at 20-40 min after injection, and time-activity curves of (18)F-FET uptake were assigned to 3 different patterns: constant increase; peak at greater than 20-40 min after injection, followed by a plateau; and early peak (≤ 20 min), followed by a constant descent. The diagnostic accuracy of (18)F-FET PET was assessed by receiver-operating-characteristic curve analyses using histology or clinical course as a reference.. In patients with newly diagnosed cerebral lesions, the highest accuracy (77%) to detect neoplastic tissue (19/26 patients) was obtained when the maximum TBR was 1.7 or greater (area under the curve, 0.80 ± 0.09; sensitivity, 79%; specificity, 71%; positive predictive value, 88%; P = 0.02). For diagnosing tumor progression or recurrence, the highest accuracy (82%) was obtained when curve patterns 2 or 3 were present (area under the curve, 0.80 ± 0.11; sensitivity, 75%; specificity, 90%; positive predictive value, 90%; P = 0.02). During chemotherapy, a decrease of TBRs was associated with a stable clinical course, and in 2 patients PET detected residual tumor after presumably complete tumor resection.. Our findings suggest that (18)F-FET PET can add valuable information for clinical decision making in pediatric brain tumor patients.

Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Disease Progression; Female; Humans; Infant; Male; Neoplasm, Residual; Positron-Emission Tomography; Recurrence; Sensitivity and Specificity; Tyrosine

We sought to assess the impact of amino-acid (18)F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET) on the volumetric target definition for radiation therapy of high-grade glioma versus the current standard using MRI alone. Specifically, we investigated the influence of tumor grade, MR-defined tumor volume, and the extent of surgical resection on PET positivity.. Fifty-four consecutive high-grade glioma patients (World Health Organization grades III-IV) with confirmed histology were scanned using FET-PET/CT and T1 and T2/fluid attenuated inversion recovery MRI. Gross tumor volume and clinical target volumes (CTVs) were defined in a blinded fashion based on MRI and subsequently PET, and volumetric analysis was performed. The extent of the surgical resection was reviewed using postoperative MRI.. Overall, for ∼ 90% of the patients, the PET-positive volumes were encompassed by T1 MRI with contrast-defined tumor plus a 20-mm margin. The tumor volume defined by PET was larger for glioma grade IV (P < .001) and smaller for patients with more extensive surgical resection (P = .004). The margin required to be added to the MRI-defined tumor in order to fully encompass the FET-PET positive volume tended to be larger for grade IV tumors (P = .018).. With an unchanged CTV margin and by including FET-PET for gross tumor volume definition, the CTV will increase moderately for most patients, and quite substantially for a minority of patients. Patients with grade IV glioma were found to be the primary candidates for PET-guided radiation therapy planning.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Tyrosine; Young Adult

Histopathological examination is the standard for grading and determination of diagnosis in intrinsic brain tumors though the possibility of malignization and tumor heterogeneity always bears the possibility of tumor under-grading or misjudgement regarding the estimation of prognosis. The aim of the present study was to evaluate the use of (18)F-FET-PET (FET-PET) for the grading and estimation of prognosis in newly diagnosed patients with intracranial gliomas in a clinical setting.. Patients who were treated for a newly diagnosed intracranial glioma between January 2007 and May 2012, and had a preoperative FET-PET and MRI scan between were included. The ratio of counts in a tumor VOI (volume of interest) with maximum uptake to the respective counts in a background VOI was calculated to provide the tumor-to-normal (T/N) ratio. The clinical and histopathological data (tumor grading, pre- and postoperative neurological status, Karnofsky Performance Status Scale scores, and overall survival rates) were recorded.. One hundred fifty-two patients (39 WHO II, 26 WHO III, 87 WHO IV) were included. The median T/N ratio was 2.81 (1.1-8.1). The median T/N ratio of low-grade glioma patients was 1.65 (1.1-3.7), and 3.14 (1.61-8.1, p<0.001) in high-grade glioma patients. The median survival for patients with WHO III tumors was 22.8 months (95% CI: 15.87%-NA) and 13.23 months (95% CI: 10.83-15.6.%) for patients with WHO IV tumors (p=0.0001). For T/N≤1.6, no deaths were recorded; for 1.63, median survival was 14.0 months (95% CI: 11.7-16.2%, p<0.001). The test of the maximally selected log-rank statistic resulted in a T/N ratio of 1.88 as the cut-off value, with the greatest difference in overall survival between patients with longer and shorter survival. The ROC curve for differentiation of low- vs. high-grade tumors with regard to the T/N ratio showed an area under the curve (AUC) of 0.903. Regarding the prognostic validity for overall survival ROC-curves for 12-month, 24-month and 48-month survival display a higher validity for the WHO-classification than for the imaging modalities though with an AUC of 0.847 for the 48-month survival T/N ratio and MRI contrast-enhancement have a high prognostic value as well.. Our study suggests that FET-PET can predict prognosis and survival in patients harboring intracranial gliomas and serves as a valuable tool to supplement the established clinical and histopathological parameters.

Topics: Adult; Aged; Area Under Curve; Brain Neoplasms; Female; Follow-Up Studies; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; ROC Curve; Tyrosine

We aimed to evaluate the diagnostic potential of dual-time-point imaging with positron emission tomography (PET) using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) for non-invasive grading of cerebral gliomas compared with a dynamic approach.. Thirty-six patients with histologically confirmed cerebral gliomas (21 primary, 15 recurrent; 24 high-grade, 12 low-grade) underwent dynamic PET from 0 to 50 min post-injection (p.i.) of (18)F-FET, and additionally from 70 to 90 min p.i. Mean tumour-to-brain ratios (TBRmean) of (18)F-FET uptake were determined in early (20-40 min p.i.) and late (70-90 min p.i.) examinations. Time-activity curves (TAC) of the tumours from 0 to 50 min after injection were assigned to different patterns. The diagnostic accuracy of changes of (18)F-FET uptake between early and late examinations for tumour grading was compared to that of curve pattern analysis from 0 to 50 min p.i. of (18)F-FET.. The diagnostic accuracy of changes of the TBRmean of (18)F-FET PET uptake between early and late examinations for the identification of HGG was 81% (sensitivity 83%; specificity 75%; cutoff - 8%; p < 0.001), and 83% for curve pattern analysis (sensitivity 88%; specificity 75%; p < 0.001).. Dual-time-point imaging of (18)F-FET uptake in gliomas achieves diagnostic accuracy for tumour grading that is similar to the more time-consuming dynamic data acquisition protocol.. • Dual-time-point imaging is equivalent to dynamic FET PET for grading of gliomas. • Dual-time-point imaging is less time consuming than dynamic FET PET. • Costs can be reduced due to higher patient throughput. • Reduced imaging time increases patient comfort and sedation might be avoided. • Quicker image interpretation is possible, as no curve evaluation is necessary.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Physical Examination; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Tyrosine

We evaluated the diagnostic value of static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET parameters in patients with progressive or recurrent glioma.. We retrospectively analyzed 132 dynamic (18)F-FET PET and conventional MRI scans of 124 glioma patients (primary World Health Organization grade II, n = 55; grade III, n = 19; grade IV, n = 50; mean age, 52 ± 14 y). Patients had been referred for PET assessment with clinical signs and/or MRI findings suggestive of tumor progression or recurrence based on Response Assessment in Neuro-Oncology criteria. Maximum and mean tumor/brain ratios of (18)F-FET uptake were determined (20-40 min post-injection) as well as tracer uptake kinetics (ie, time to peak and patterns of the time-activity curves). Diagnoses were confirmed histologically (95%) or by clinical follow-up (5%). Diagnostic accuracies of PET and MR parameters for the detection of tumor progression or recurrence were evaluated by receiver operating characteristic analyses/chi-square test.. Tumor progression or recurrence could be diagnosed in 121 of 132 cases (92%). MRI and (18)F-FET PET findings were concordant in 84% and discordant in 16%. Compared with the diagnostic accuracy of conventional MRI to diagnose tumor progression or recurrence (85%), a higher accuracy (93%) was achieved by (18)F-FET PET when a mean tumor/brain ratio ≥2.0 or time to peak <45 min was present (sensitivity, 93%; specificity, 100%; accuracy, 93%; positive predictive value, 100%; P < .001).. Static and dynamic (18)F-FET PET parameters differentiate progressive or recurrent glioma from treatment-related nonneoplastic changes with higher accuracy than conventional MRI.

Topics: Brain Neoplasms; Disease Progression; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Retrospective Studies; Sensitivity and Specificity; Tyrosine

O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is an established tracer for brain tumour imaging. (18)F-FET kinetics in gliomas appear to have potential for tumour grading, but the mechanisms remain unclear. The aim of this study was to explore the relationship between regional cerebral blood flow (rCBF) as measured by arterial spin labelling MRI and the kinetic behaviour of (18)F-FET PET in cerebral gliomas.. Twenty patients with cerebral gliomas were investigated using arterial spin labelling MRI and dynamic (18)F-FET PET. Time-activity curves (TACs) of (18)F-FET uptake were analysed in 33 different tumour regions. The slopes of TAC during the early (0-5 min; slopeup) and late phases of tracer uptake (17-50 min; slopedown) were fitted using linear regression lines. In addition, TACs of each lesion were assigned to different curve patterns. Furthermore, we calculated tumour-to-brain ratios of (18)F-FET uptake. The relationship between (18)F-FET parameters and rCBF was determined.. (18)F-FET uptake in the early phase (slopeup) showed a significant correlation with rCBF (r=0.4; P=0.02). In contrast, both slopedown and TAC patterns showed no significant correlation with rCBF. Furthermore, a significant correlation was found between rCBF and tumour-to-brain ratio (r=0.53; P=0.002).. There is a relationship between rCBF and (18)F-FET uptake in cerebral gliomas in the initial uptake phase, but the kinetic behaviour of (18)F-FET uptake in the late phase is not significantly influenced by rCBF. Thus, the differential kinetic pattern of (18)F-FET uptake in high-grade and low-grade gliomas appears to be determined by factors other than rCBF.

Topics: Adult; Aged; Biological Transport; Brain Neoplasms; Cerebrovascular Circulation; Female; Glioma; Humans; Kinetics; Male; Middle Aged; Positron-Emission Tomography; Tyrosine

To evaluate the prognostic value of O-(2-[(18)F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II-IV gliomas.. We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax.. Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p = 0.005) and progression-free survival (p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p = 0.001) and SUVmax ≥ 2.6 (p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean.. In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval.

Topics: Adolescent; Adult; Aged; Brain; Brain Neoplasms; Disease-Free Survival; Female; Glioma; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Time Factors; Tyrosine; Young Adult

Low-grade gliomas (LGGs) may harbor malignant foci, which are characterized by increased tumor cellularity and angiogenesis. We used diffusion-weighted MR imaging (apparent diffusion coefficient [ADC]) and PET with the amino acid O-(2-(18)F-fluorethyl)-L-tyrosine ((18)F-FET) to search for focal changes of diffusion (ADC) and amino acid uptake and to investigate whether focal changes in these parameters colocalize within LGGs.. We retrospectively selected 18 patients with nonenhancing LGG. All patients had undergone (18)F-FET PET and MR imaging for preoperative evaluation or for therapy monitoring in recurrent or progressive LGG. Region-of-interest analysis was performed to compare (18)F-FET uptake and ADC values in areas with focal intratumoral maximum metabolic activity and diffusion restriction and between tumor and normal brain. (18)F-FET uptake was normalized to the mean cerebellar uptake (ratio). ADC values were also compared with the (18)F-FET uptake on a voxel-by-voxel basis across the whole tumor.. The mean focal maximum (mean ± SD, 1.69 ± 0.85) and global (18)F-FET uptake in tumors (1.14 ± 0.41) exceeded that of normal cortex (0.85 ± 0.09) and cerebrospinal fluid (0.82 ± 0.20). ADC values in the area with most restricted diffusion (1.07 ± 0.22 × 10(-3) mm(2)/s) and in the whole tumor (1.38 ± 0.27 × 10(-3) mm(2)/s) were in the range between normal cortex (0.73 ± 0.06 × 10(-3) mm(2)/s) and cerebrospinal fluid (2.84 ± 0.09 × 10(-3) mm(2)/s). (18)F-FET uptake did not correlate with corresponding (colocalizing) ADC values, either in the area with focal maximum metabolic activity or in the area with most restricted diffusion or in the whole tumor.. There is no congruency between (18)F-FET uptake and diffusivity in nonenhancing LGG. Diffusion restriction in these tumors most likely represents changes in brain and tumor cell densities as well as alteration of water distribution and is probably not directly correlated with the density of tumor cells.

Topics: Adult; Aged; Amino Acids; Brain Neoplasms; Cerebellar Neoplasms; Cerebellum; Diffusion; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tyrosine

PET using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) allows improved imaging of tumor extent of cerebral gliomas in comparison to MRI. In experimental brain infarction and hematoma, an unspecific accumulation of (18)F-FET has been detected in the area of reactive astrogliosis which is a common cellular reaction in the vicinity of cerebral gliomas. The aim of this study was to investigate possible (18)F-FET uptake in the area of reactive gliosis in the vicinity of untreated and irradiated rat gliomas.. F98-glioma cells were implanted into the caudate nucleus of 33 Fisher CDF rats. Sixteen animals remained untreated and in 17 animals the tumor was irradiated by Gamma Knife 5-8 days after implantation (2/50 Gy, 3/75 Gy, 6/100 Gy, 6/150 Gy). After 8-17 days of tumor growth the animals were sacrificed following injection of (18)F-FET. Brains were removed, cut in coronal sections and autoradiograms of (18)F-FET distribution were produced and compared with histology (toluidine blue) and reactive astrogliosis (GFAP staining). (18)F-FET uptake in the tumors and in areas of reactive astrocytosis was evaluated by lesion to brain ratios (L/B).. Large F98-gliomas were present in all animals showing increased (18)F-FET-uptake which was similar in irradiated and non-irradiated tumors (L/B: 3.9 ± 0.8 vs. 4.0 ± 1.3). A pronounced reactive astrogliosis was noted in the vicinity of all tumors that showed significantly lower (18)F-FET-uptake than the tumors (L/B: 1.5 ± 0.4 vs. 3.9 ± 1.1). The area of (18)F-FET-uptake in the tumor was congruent with histological tumor extent in 31/33 animals. In 2 rats irradiated with 150 Gy, however, high (18)F-FET uptake was noted in the area of astrogliosis which led to an overestimation of the tumor size.. Reactive astrogliosis in the vicinity of gliomas generally leads to only a slight (18)F-FET-enrichment that appears not to affect the correct definition of tumor extent for treatment planning.

Topics: Animals; Biological Transport; Brain; Brain Neoplasms; Cell Line, Tumor; False Positive Reactions; Glioma; Gliosis; Male; Positron-Emission Tomography; Rats; Tyrosine

Modern radiotherapy (RT) techniques such as stereotactic RT, intensity-modulated RT, or particle irradiation allow local dose escalation with simultaneous sparing of critical organs. Several trials are currently investigating their benefit in glioma reirradiation and boost irradiation. Target volume definition is of critical importance especially when steep dose gradient techniques are employed. In this manuscript we investigate the impact of O-(2-(F-18)fluoroethyl)-l-tyrosine-positron emission tomography/computer tomography (FET-PET/CT) on target volume definition in low and high grade glioma patients undergoing either first or re-irradiation with particles.. We investigated volumetric size and uniformity of magnetic resonance imaging (MRI)- vs. FET-PET/CT-derived gross tumor volumes (GTVs) and planning target volumes (PTVs) of 41 glioma patients. Clinical cases are presented to demonstrate potential benefits of integrating FET-PET/CT-planning into daily routine.. Integrating FET-uptake into the delineation of GTVs yields larger volumes. Combined modality-derived PTVs are significantly enlarged in high grade glioma patients and in case of primary RT. The congruence of MRI and FET signals for the identification of glioma GTVs is poor with mean uniformity indices of 0.39. MRI-based PTVs miss 17% of FET-PET/CT-based GTVs. Non significant alterations were detected in low grade glioma patients and in those undergoing reirradiation.. Target volume definition for malignant gliomas during initial RT may yield significantly differing results depending upon the imaging modality, which the contouring process is based upon. The integration of both MRI and FET-PET/CT may help to improve GTV coverage by avoiding larger incongruences between physical and biological imaging techniques. In low grade gliomas and in cases of reirradiation, more studies are needed in order to investigate a potential benefit of FET-PET/CT for planning of RT.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Tomography, X-Ray Computed; Tyrosine; Young Adult

Monitoring of radiochemotherapy (RCX) in patients with glioblastoma is difficult because unspecific alterations in magnetic resonance imaging with contrast enhancement can mimic tumor progression. Changes in tumor to brain ratios (TBRs) in positron emission tomography (PET) using O-(2-¹⁸fluoroethyl)-l-tyrosine (¹⁸F-FET) after RCX with temozolomide of patients with glioblastoma have been shown to be valuable parameters to predict survival. The kinetic behavior of ¹⁸F-FET in the tumors is another promising parameter to analyze tumor metabolism. In this study, we investigated the predictive value of dynamic ¹⁸F-FET PET during RCX of glioblastoma. Time-activity curves (TACs) of ¹⁸F-FET uptake of 25 patients with glioblastoma were evaluated after surgery (FET-1), early (7-10 days) after completion of RCX (FET-2), and 6 to 8 weeks later (FET-3). Changes in the time to peak (TTP) and the slope of the TAC (10-50 minutes postinjection) were analyzed and related to survival. Changes in kinetic parameters of ¹⁸F-FET uptake after RCX showed no relationship with survival time. In contrast, the high predictive value of changes of TBR to predict survival was confirmed. We conclude that dynamic ¹⁸F-FET PET does not provide additional prognostic information during RCX. Static ¹⁸F-FET PET imaging (20-40 minutes postinjection) appears to be sufficient for this purpose and reduces costs.

Topics: Adult; Aged; Area Under Curve; Brain Neoplasms; Female; Fluorine Radioisotopes; Glioblastoma; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Tyrosine

To assess the sensitivity and specificity of [(18)F]-fluoro-ethyl-l-tyrosine ((18)F-FET) PET in brain tumors and various non-neoplastic neurologic diseases.. We retrospectively evaluated (18)F-FET PET scans from 393 patients grouped into 6 disease categories according to histology (n = 299) or distinct MRI findings (n = 94) (low-grade/high-grade glial/nonglial brain tumors, inflammatory lesions, and other lesions). (18)F-FET PET was visually assessed as positive or negative. Maximum lesion-to-brain ratios (LBRs) were calculated and compared with MRI contrast enhancement (CE), which was graded visually on a 3-point scale (no/moderate/intense).. Sensitivity and specificity for the detection of brain tumor were 87% and 68%, respectively. Significant differences in LBRs were detected between high-grade brain tumors (LBR, 2.04 ± 0.72) and low-grade brain tumors (LBR, 1.52 ± 0.70; P < .001), as well as among inflammatory (LBR, 1.66 ± 0.33; P = .056) and other brain lesions (LBR, 1.10 ± 0.37; P < .001). Gliomas (n = 236) showed (18)F-FET uptake in 80% of World Health Organization (WHO) grade I, 79% of grade II, 92% of grade III, and 100% of grade IV tumors. Low-grade oligodendrogliomas, WHO grade II, had significantly higher (18)F-FET uptakes than astrocytomas grades II and III (P = .018 and P = .015, respectively). (18)F-FET uptake showed a strong association with CE on MRI (P < .001) and was also positive in 52% of 157 nonglial brain tumors and nonneoplastic brain lesions.. (18)F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood-brain barrier and (18)F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood-Brain Barrier; Brain Neoplasms; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity; Tyrosine; Young Adult

The aim of this study was to investigate the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET for differentiating local recurrent brain metastasis from radiation necrosis after radiation therapy because the use of contrast-enhanced MRI for this issue is often difficult.. Thirty-one patients (mean age ± SD, 53 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 40) on MRI after radiation therapy of brain metastases were investigated with dynamic (18)F-FET PET. Maximum and mean tumor-to-brain ratios (TBR(max) and TBR(mean), respectively; 20-40 min after injection) of (18)F-FET uptake were determined. Time-activity curves were generated, and the time to peak (TTP) was calculated. Furthermore, time-activity curves of each lesion were assigned to one of the following curve patterns: (I) constantly increasing (18)F-FET uptake, (II) (18)F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau, and (III) (18)F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBR(max) and TBR(mean) of (18)F-FET uptake and the curve patterns for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or Fisher exact test for 2 × 2 contingency tables using subsequent histologic analysis (11 lesions in 11 patients) or clinical course and MRI findings (29 lesions in 20 patients) as reference.. Both TBR(max) and TBR(mean) were significantly higher in patients with recurrent metastasis (n = 19) than in patients with radiation necrosis (n = 21) (TBR(max), 3.2 ± 0.9 vs. 2.3 ± 0.5, P < 0.001; TBR(mean), 2.1 ± 0.4 vs. 1.8 ± 0.2, P < 0.001). The diagnostic accuracy of (18)F-FET PET for the correct identification of recurrent brain metastases reached 78% using TBR(max) (area under the ROC curve [AUC], 0.822 ± 0.07; sensitivity, 79%; specificity, 76%; cutoff, 2.55; P = 0.001), 83% using TBR(mean) (AUC, 0.851 ± 0.07; sensitivity, 74%; specificity, 90%; cutoff, 1.95; P < 0.001), and 92% for curve patterns II and III versus curve pattern I (sensitivity, 84%; specificity, 100%; P < 0.0001). The highest accuracy (93%) to diagnose local recurrent metastasis was obtained when both a TBR(mean) greater than 1.9 and curve pattern II or III were present (AUC, 0.959 ± 0.03; sensitivity, 95%; specificity, 91%; P < 0.001).. Our findings suggest that the combined evaluation of the TBR(mean) of (18)F-FET uptake and the pattern of the time-activity curve can differentiate local brain metastasis recurrence from radionecrosis with high accuracy. (18)F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Topics: Adolescent; Adult; Aged; Biological Transport; Brain Neoplasms; Diagnosis, Differential; Humans; Male; Middle Aged; Necrosis; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiation Injuries; ROC Curve; Tyrosine; Young Adult

The aim of the present study is to determine new positron emission tomography (PET) imaging-related factors predictive of progression-free survival as well as survival in patients with recurrent malignant glioma (MG) prior to and after re-irradiation. Fifty-six patients with recurrent MG who underwent re-irradiation treatment and pretherapeutic dynamic [(18)F]-fluoroethyl-L-tyrosine (FET)-PET scan were retrospectively analyzed. The prognostic value of different parameters, such as biological tumor volume, maximal tumor uptake (SUV(max)/BG), mean tumor uptake (SUV(mean)/BG), as well as uptake kinetics, was evaluated. [(18)F]FET uptake kinetics was classified according to a five-point rating as category G(1-2) (strongly/mainly increasing kinetics), G(3) (mixed 1:1), or G(4-5) (mainly/strongly decreasing kinetics). Patients within the pretherapeutic kinetic group G(4-5) had significantly worse survival than the other two groups (p = 0.01). Multivariate analysis revealed that histologic grade, Karnofsky Performance Score (KPS), and kinetic group were independent significant predictors for survival after re-irradiation. The uptake kinetics of [(18)F]FET-PET is an independent determinant of overall and to a lesser extent also progression-free survival. Thus, [(18)F]FET-PET kinetics may provide valuable additional prognostic information for treatment decisions.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Glioma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Salvage Therapy; Survival Rate; Tyrosine; Young Adult

The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that (18)F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and α-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose-boronophenylalanine (BPA). Therefore, FET-PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT.

Topics: Animals; Boron Neutron Capture Therapy; Brain Neoplasms; Disease Models, Animal; Glioma; Multimodal Imaging; Positron-Emission Tomography; Rats; Tomography, X-Ray Computed; Tyrosine

Resection is considered as essential for the efficacy of modern adjuvant treatment of glioblastoma multiforme (GBM). Previous studies have indicated that amino acid PET is more specific than contrast enhancement on MRI for detecting residual tumor tissue after surgery. In a prospective study we investigated the prognostic impact of postoperative tumor volume and tumor/brain ratios (TBR) in PET using O-(2-[(18)F]fluoroethyl)-l-tyrosine (FET) in comparison with MRI.. Forty-four patients with GBM were investigated by FET PET and MRI after surgery. Tumor volume in FET PET with a tumor/brain ratio (TBR)>1.6 and a TBR>2, mean and maximum TBR and gadolinium contrast-enhancement on MRI (Gd-volume) were determined. Thereafter patients received a fractionated radiotherapy with concomitant temozolomide (RCX). The median follow-up was 15.4 (3-35) months. The prognostic value of postoperative residual tumor volume in FET PET, TBR(mean,) TBR(max) and Gd-volume was evaluated using Kaplan-Maier estimates for disease-free survival (DFS) and overall survival (OS).. Postoperative tumor volume in FET PET had a significant independent influence on OS and DFS (OS 20.0 vs. 6.9 months; DFS 9.6 vs. 5.1 months, p<0.001; cut-off 25 ml). Similar results were observed when a TBR ≥ 2 (cut-off 10 ml) was used to define the tumor volume in (18)F-FET PET. The TBR(mean) and TBR(max) of FET uptake had a significant influence on DFS (p<0.05). Gd-volume in MRI had significant effect on OS and DFS in the univariate analysis. No independent significant influence in OS or DFS could be observed for Gd-volume in MRI.. Our data indicate that the tumor volume in FET PET after surgery of GBM has a strong prognostic impact for these patients. FET PET appears to be helpful to determine the residual tumor volume after surgery of GBM and may serve as a valuable tool for optimal planning of radiation treatment.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Combined Modality Therapy; Contrast Media; Cranial Irradiation; Dacarbazine; Dose Fractionation, Radiation; Female; Fluorine Radioisotopes; Gadolinium DTPA; Glioblastoma; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm, Residual; Positron-Emission Tomography; Prognosis; Proportional Hazards Models; Prospective Studies; Survival Rate; Temozolomide; Treatment Outcome; Tumor Burden; Tyrosine

L-[methyl-(11)C]methionine (MET)-positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of (11)C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is labeled with (18)F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI).. We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion-to-gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up.. There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p < 0.001), respectively. Image contrast was similar for MET- and FET-PET (lesion-to-gray matter ratios of 2.36 ± 1.01 and 2.33 ± 0.77, respectively). Mean GTV in 17 glioma patients was not significantly different on MET- and FET-PET. Both MET- and FET-PET delineated tumor tissue outside of MRI changes. Both tracers provided differentiated tumor tissue and treatment-related changes with a sensitivity of 91% at a specificity of 100%.. O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.

Topics: Brain; Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Methionine; Neoplasm Recurrence, Local; Neoplasm, Residual; Positron-Emission Tomography; Prospective Studies; Sensitivity and Specificity; Time Factors; Tumor Burden; Tyrosine

The objective of this study was to compare MRI response assessment with metabolic O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG).. Eleven patients with rHGG were treated biweekly with bevacizumab-irinotecan. MR images and (18)F-FET PET scans were obtained at baseline and at follow-up 8-12 wk after treatment onset. MRI treatment response was evaluated by T1/T2 volumetry according to response assessment in neurooncology (RANO) criteria. For (18)F-FET PET evaluation, an uptake reduction of more than 45% calculated with a standardized uptake value of more than 1.6 was defined as a metabolic response (receiver-operating-characteristic curve analysis). MRI and (18)F-FET PET volumetry results and response assessment were compared with each other and in relation to progression-free survival (PFS) and overall survival (OS).. At follow-up, MR images showed partial response in 7 of 11 patients (64%), stable disease in 2 of 11 patients (18%), and tumor progression in 2 of 11 patients (18%). In contrast, (18)F-FET PET revealed 5 of 11 metabolic responders (46%) and 6 of 11 nonresponders (54%). MRI and (18)F-FET PET showed that responders survived significantly longer than did nonresponders (10.24 vs. 4.1 mo, P = 0.025, and 7.9 vs. 2.3 mo, P = 0.015, respectively). In 4 patients (36.4%), diagnosis according to RANO criteria and (18)F-FET PET was discordant. In these cases, PET was able to detect tumor progression earlier than was MRI.. In rHGG patients undergoing antiangiogenic treatment, (18)F-FET PET seems to be predictive for treatment failure in that it contributes important information to response assessment based solely on MRI and RANO criteria.

Topics: Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Astrocytoma; Bevacizumab; Brain Neoplasms; Camptothecin; Combined Modality Therapy; Disease-Free Survival; Female; Glioma; Humans; Image Processing, Computer-Assisted; Irinotecan; Magnetic Resonance Imaging; Male; Middle Aged; Nervous System Diseases; Positron-Emission Tomography; Postoperative Complications; Predictive Value of Tests; Radiopharmaceuticals; Retrospective Studies; Survival Analysis; Treatment Failure; Tyrosine; Ultrasonography

The aims of this study were to investigate and categorize peritumoral fiber tract alterations while considering changes in metabolism and integrity of fiber structures using multimodal neuroimaging-that is, PET with O-(2-(18)F-fluoroethyl)-l-tyrosine and diffusion tensor imaging evaluated by fiber density mapping-and to correlate categories of fiber alterations with preoperative neurologic deficits and postoperative course.. We examined 26 patients with cerebral gliomas. Fiber density data were used to segment peritumoral fiber structures and were coregistered to anatomic MR images and PET data. Fiber density and O-(2-(18)F-fluoroethyl)-l-tyrosine uptake values were evaluated as ipsilateral-to-contralateral ratios. Four metabolic categories were defined on the basis of O-(2-(18)F-fluoroethyl)-l-tyrosine values: tumor-infiltrated tissue, reactive tissue (astrogliosis and microglial activation), normal brain tissue, and tissue with attenuated amino acid metabolism. Fiber density values were grouped in 3 categories for structural integrity: compressed, normal, and attenuated fibers.. We evaluated and classified 103 peritumoral fiber structures with 10 patterns of fiber tract alterations. Fiber structures in tumor-infiltrated, reactive, and normal brain tissue showed compressed fibers, displaced fibers, and (partly) destroyed fibers, respectively. Attenuated amino acid metabolism was associated only with attenuated fiber density. Thirteen patients showed white matter-related neurologic deficits (paresis, hypoesthesia, aphasia, or anopia) as initial symptoms. Three patients showed tumor infiltration in the corresponding fiber tracts; all the others had reactive or normal brain tissue. Fiber structures were compressed or attenuated but not normal. The 3 patients with tumor infiltration in the corresponding fiber tracts and 1 with compressed fibers in normal brain showed no improvements or worsening of the deficits in the postoperative course. Eight patients with the corresponding fiber tracts in reactive or normal brain areas showed improvement of deficits. One patient underwent biopsy only.. Our multimodal neuroimaging approach provides complementary information and more detailed understanding of peritumoral fiber tract alterations in gliomas which are more complex as described so far. We presented a classification model for systematic assessment of these alterations that may be helpful for treatment planning and prediction of patients' prognoses.

Topics: Adult; Aged; Brain Neoplasms; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Female; Fluorine Radioisotopes; Glioma; Humans; Magnetic Resonance Imaging; Male; Medical Oncology; Middle Aged; Nervous System Diseases; Neurology; Neurons; Positron-Emission Tomography; Prognosis; Tyrosine

The aim of this prospective pilot study in patients with suspected or known brain tumour was to establish the diagnostic value of O-(2-[(18)F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) when compared to fluorine-18 fluorodeoxyglucose (FDG) PET. Twenty-five FET PET and FDG PET scans were performed on 21 consecutive patients within 24 months. Final malignant pathology included 11 glioma (eight low-grade, three high grade), two lymphoma, one olfactory ganglioneuroblastoma, one anaplastic meningioma. Benign pathology included two encephalitis and one cortical dysplasia. Definitive pathology was not available in three patients. The accuracy of PET was determined by subsequent surgical histopathology in 12 and clinical/imaging course in nine patients. Median follow-up period was 20 months. FET sensitivity was 93%, specificity 100%, accuracy 96%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91%. FDG sensitivity was 27%, specificity 90%, accuracy 52%, PPV 80% and NPV 45%. FET PET is more accurate than FDG PET for detecting malignant brain lesions, especially low-grade gliomas.

Topics: Adult; Aged; Brain; Brain Neoplasms; Diagnosis, Differential; Diagnostic Errors; Female; Fluorodeoxyglucose F18; Glioma; Humans; Lymphoma; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Prospective Studies; Radioisotopes; Reproducibility of Results; Sensitivity and Specificity; Tyrosine; Young Adult

The aim of this study was to evaluate the clinical value of the use of O-(2-[(18)F]fluoroethyl)-L: -tyrosine (FET) positron emission tomography (PET)/computed tomography (CT) in patients of a neurological clinic for evaluation of brain lesions newly diagnosed by magnetic resonance imaging (MRI).. We evaluated 88 patients (44 women and 44 men) with a mean age of 50 +/- 19 years who were sent consecutively for evaluation of an intracerebral mass or lesion observed by MRI from 2006 to 2008. Hospitalization was necessary due to neurological clinical symptoms. Images were obtained by PET/CT 30 min after i.v. injection of 185 MBq FET. Coregistration with MRI was done by HERMES workstation.. FET uptake above the cortical level was observed in 60 patients. Neurosurgery was performed in 60 patients (51 with FET-positive imaging); 36 high-grade and 19 low-grade tumours were verified histologically. The sensitivity of FET PET for high-grade tumours (WHO III-IV) was 94% in this setting. Among the low-grade brain tumours (WHO I-II) 13 of 19 were FET positive, which indicates a sensitivity of 68%. Five of ten (50%) astrocytomas I and II could not be visualized by FET. Histological data were not provided for 28 of 88 patients, so the diagnostic approach is based upon longitudinal observation. Radiological and/or clinical control was done at a median of 7 months later. Three patients (all FET positive) died a few months after the examination because of rapid progression of the malignant brain tumour. A malignant entity could be excluded in the other 25 patients. Considering the whole cohort of 88 patients, 43 patients with malignant tumour could be identified, including high-grade glioma, intracerebral lymphoma (n = 1) and metastasis (n = 3). The sensitivity of FET PET for detecting a malignant tumour entity was 93%. We observed two false-positive cases with postischaemic lesions. Remarkably, the two patients with cerebral gliomatosis were false-negative on FET PET imaging. The negative predictive value for a malignant entity was calculated to be 89%.. Our results indicate a high sensitivity of FET PET for detecting high-grade glioma in patients with neurological symptoms and recently observed brain lesions by MRI. In the setting of evaluating new brain lesions of unknown significance via FET PET a negative image can encourage a wait and see strategy-of course in accordance with the clinical picture and morphological imaging.

Topics: Adult; Aged; Brain Neoplasms; Female; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Radiography; Retrospective Studies; Tyrosine

To investigate the potential of (18)F-fluoroethyltyrosine-positron emission tomography-((18)F-FET-PET-)based dose painting by numbers with protons.. Due to its high specificity to brain tumor cells, FET has a high potential to serve as a target for dose painting by numbers. Biological image-based dose painting might lead to an inhomogeneous dose prescription. For precise treatment planning of such a prescribed dose, an intensity-modulated radiotherapy (IMRT) algorithm including a Monte Carlo dose-calculation algorithm for spot-scanning protons was used. A linear tracer uptake to dose model was used to derive a dose prescription from the (18)F-FET-PET. As a first investigation, a modified modulation transfer function (MTF) of protons was evaluated and compared to the MTF of photons. In a clinically adapted planning study, the feasibility of (18)F-FET-PET-based dose painting with protons was demonstrated using three patients with glioblastome multiforme. The resulting dose distributions were evaluated by means of dose-difference and dose-volume histograms and compared to IMRT data.. The MTF for protons was constantly above that for photons. The standard deviations of the dose differences between the prescribed and the optimized dose were smaller in case of protons compared to photons. Furthermore, the escalation study showed that the doses within the subvolumes identified by biological imaging techniques could be escalated remarkably while the dose within the organs at risk was kept at a constant level.. The presented investigation fortifies the feasibility of (18)F-FET-PET-based dose painting with protons.

Topics: Algorithms; Brain Neoplasms; Fluorine Radioisotopes; Glioblastoma; Humans; Linear Energy Transfer; Monte Carlo Method; Photons; Positron-Emission Tomography; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Tyrosine

Standard magnetic resonance imaging (MRI) does not depict the true extent of tumour cell invasion in gliomas. We investigated the feasibility of advanced imaging methods, i.e. diffusion tensor imaging (DTI), fibre tracking and O-(2-[(18)F]-fluoroethyl)-L: -tyrosine ((18)F-FET) PET, for the detection of tumour invasion into white matter structures not visible in routine MRI.. DTI and fibre tracking was performed on ten patients with gliomas, WHO grades II-IV. Five patients experienced preoperative sensorimotor deficits. The ratio of fractional anisotropy (FA) between the ipsilateral and contralateral pyramidal tract was calculated. Twenty-one stereotactic biopsies from five patients were histopathologically evaluated for the absolute numbers and percentages of tumour cells. (18)F-FET PET scans were performed and the bilateral ratio [ipsilateral-to-contralateral ratio (ICR)] of (18)F-FET-uptake was calculated for both cross-sections of pyramidal tracts and biopsy sites.. The FA ratio within the pyramidal tract was lower in patients with sensorimotor deficits (0.61-1.06) compared with the FA ratio in patients without sensorimotor deficits (0.92-1.06). In patients with preoperative sensorimotor deficits, we found a significantly (p = 0.028) higher ICR of (18)F-FET uptake (1.01-1.59) than in patients without any deficits (0.96-1.08). The ICR of (18)F-FET-uptake showed a strong correlation (r = 0.696, p = 0.001) with the absolute number of tumour cells and a moderate correlation (r = 0.535, p = 0.012) with the percentage of tumour cells.. Our data show an association between preoperative sensorimotor deficits, increased (18)F-FET uptake and decreased FA ratio in the pyramidal tract. We demonstrated a correlation between tumour invasion and (18)F-FET uptake. These findings may help to distinguish between edema versus tumour-associated neurological deficits and could prevent the destruction of important structures, like the pyramidal tract, during tumour operations by allowing more precise preoperative planning.

Topics: Adult; Aged; Brain; Brain Neoplasms; Contrast Media; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Male; Middle Aged; Movement Disorders; Neoplasm Invasiveness; Positron-Emission Tomography; Predictive Value of Tests; Pyramidal Tracts; Radiography; Sensation Disorders; Sensitivity and Specificity; Tyrosine

Malignant gliomas are highly infiltrative tumours with a fatal prognosis. F18-fluoroethyl-tyrosine (FET)-positron emission tomography (PET) often reveals a broader extension of these tumours compared with contrast-enhanced magnetic resonance imaging (MRI). Complete resection of the contrast-enhancing lesion is aspired. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) improved the extent of resection. In this study, we investigated whether the FET uptake correlates with the extent of resection using 5-ALA-induced fluorescence.. Thirteen patients who underwent preoperative and postoperative MRI, FET-PET and fluorescence-guided neuronavigated resection were included in this study. The areas in which intraoperative fluorescence terminated the resection were marked. After fusion of PET and MRI, the standardized uptake value (SUV) of FET related to normal brain (SUV(R)) was measured in regions of interest corresponding to resected and remaining tissue, respectively. Receiver-operating characteristic (ROC) curve analysis determined the optimal threshold of the relative SUV anticipating 5-ALA-induced fluorescence.. During resection a vivid fluorescence was present in all patients. Histology revealed glioblastomas in 11 cases, an anaplastic astrocytoma in one case and a low-grade astrocytoma in one case. The median FET SUV(R) was higher in areas corresponding to the fluorescent tumour compared with the non-fluorescent normal brain (2.321 vs 1.142, p < 0.0001, t-test). A SUV(R) greater than 1.374 predicted the fluorescence with a sensitivity of 0.87 [95% confidence interval (CI): 0.74-0.94] and a specificity of 0.94 (CI: 0.84-0.99). The area under the ROC curve was 0.9656 (CI: 0.9364-0.9948).. FET uptake predicts the 5-ALA-induced fluorescence in glioma patients. Thus, FET-PET provides useful information for planning glioma resection.

Topics: Adult; Aged; Aminolevulinic Acid; Biomarkers, Tumor; Brain Neoplasms; Female; Fluorescence; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Monitoring, Intraoperative; Neuronavigation; Neurosurgical Procedures; Positron-Emission Tomography; Predictive Value of Tests; Preoperative Care; Tyrosine

To demonstrate the feasibility of a biologically adapted dose-escalation approach to brain tumors.. Due to the specific accumulation of fluoroethyltyrosine (FET) in brain tumors, (18)F-FET-PET imaging is used to derive a voxel-by-voxel dose distribution. Although the kinetics of (18)F-FET are not completely understood, the authors regard regions with high tracer uptake as vital and aggressive tumor and use a linear dose-escalation function between SUV (standard uptake value) 3 and SUV 5. The resulting dose distribution is then planned using the inverse Monte Carlo treatment- planning system IKO. In a theoretical study, the dose range is clinically adapted from 1.8 Gy to 2.68 Gy per fraction (with a total of 30 fractions). In a second study, the maximum dose of the model is increased step by step from 2.5 Gy to 3.4 Gy to investigate whether a significant dose escalation to tracer-accumulating subvolumes is possible without affecting the shell-shaped organ at risk (OAR). For all dose-escalation levels the dose difference Delta D of each voxel inside the target volume is calculated and the mean dose difference Delta D and their standard deviation sigma Delta D are determined. The dose to the OAR is evaluated by the dose values D OAR 50% and D OAR 5%, which are the dose values not exceeded by 50% and 5% of the volume, respectively.. The inhomogeneous dose prescription is achieved with high accuracy (Delta D < 0.03 +/- 0.3 Gy/fraction). The maximum dose can be increased remarkably, without increasing the dose to the OAR (standard deviation of D OAR 50% < 0.02 Gy/fraction and of D OAR 5% < 0.05 Gy/fraction).. Assuming that regions with high tracer uptake can be interpreted as target for radiotherapy, (18)F-FET-PET-based "dose painting by numbers" applied to brain tumors is a feasible approach. The dose, and therefore potentially the chance of tumor control, can be enhanced. The proposed model can easily be transferred to other tracers and tumor entities.

Topics: Aged; Brain Neoplasms; Feasibility Studies; Female; Fluorine Radioisotopes; Glioblastoma; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Monte Carlo Method; Positron-Emission Tomography; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Tomography, X-Ray Computed; Tyrosine

To explore prospectively the positive predictive value of O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET)-PET in selected patients with a magnetic resonance imaging (MRI)-based suspicion of a glioma recurrence or progression. Methods Patients with a supratentorial glioma (initial World Health Organization (WHO) grade II, III or IV) were considered eligible if they had both an MRI-(new/progressive contrast-enhancing lesion) and FET-PET-based diagnosis of a recurrence/progression after various forms and combinations of irradiation and chemotherapy. Criterion for tumour recurrence/progression in FET-PET was a standardized uptake value (SUVmax)/Background (BG) ratio of >2.0 in the late uptake phase. All patients underwent multimodal (MRI, FET-PET) imaging-guided stereotactic biopsy. The positive predictive value was defined as the proportion of MRI and FET-PET findings indicating glioma recurrence/progression that also tested positive for tumour recurrence/progression after stereotactic biopsy.. Thirty-one patients with initially WHO grade II (17), WHO grade III (6), and grade IV glioma (8) were included. In 26 patients FET-PET results indicating tumour recurrence/progression were concordant with the biopsy results. In five patients histopathologic evaluation failed to reveal a "vital" tumour. FET-PET findings were also discordant with the radiographic and clinical follow-up in these five patients. The positive predictive value of FET-PET was 84%.. The positive predictive value of FET-PET using the standard ratio method is high, but not high enough to replace stereotactic biopsy in this highly selected study cohort. Whether the calculation of FET uptake in the early phase and/or the evaluation of uptake kinetics will improve the positive predictive value of FET-PET deserves prospective evaluation.

Topics: Adult; Aged; Biopsy; Brain Neoplasms; Cell Proliferation; Combined Modality Therapy; Disease Progression; Female; Glioma; Humans; Ki-67 Antigen; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Stereotaxic Techniques; Tyrosine

Amino acids are valuable tracers for brain tumor imaging with positron emission tomography (PET). In this study the transport of O-(2-[(18)F]fluoroethyl)-D-tyrosine (D-FET) across the blood-brain barrier (BBB) was studied with PET in anesthetized piglets and patients after subtotal resection of brain tumors and compared with O-(2-[(18)F]fluoroethyl)-L-tyrosine (L-FET) and 3-O-methyl-6-[(18)F]fluoro-L-DOPA (L-OMFD). In piglets, compartmental modeling of PET data was used to calculate the rate constants for the blood-brain (K(1)) and the brain-blood (k(2)) transfer of D-FET, L-FET and L-OMFD. In patients standardized uptake values (SUVs) were calculated in brain cortex and lesions. Additionally, affinity determinations on various amino acid transporters (LAT1, LAT2, PAT1, XPCT) were performed in vitro using unlabeled D-FET, L-FET and L-OMFD. The initial brain uptake of D-FET in piglets was more than two-fold higher than that of l-FET, whereas the initial brain uptake of D-FET in patients was similar to that of L-FET. Calculation of K(1) and k(2) from the brain uptake curves and the plasma input data in piglets revealed about 4- and 2-fold higher values for D-FET compared to L-FET and L-OMFD, respectively. The distribution volume of D-FET in the piglet brain was slightly higher than that of L-FET as it was also found for most other organs. In brain tumor patients, initial D-FET uptake in the brain was similar to that of L-FET but showed faster tracer washout. L-FET uptake remained rather constant and provided a better delineation of residual tumor than D-FET. In conclusion, our data indicate considerable differences of stereoselective amino acid transport at the BBB in different species. Therefore, the results from animal experiments concerning BBB amino acid transport may not be transferable to humans.

Topics: Adult; Animals; Biological Transport; Blood-Brain Barrier; Brain; Brain Neoplasms; Contrast Media; Dihydroxyphenylalanine; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Positron-Emission Tomography; Stereoisomerism; Swine; Tissue Distribution; Tyrosine

Targeting extracellular structures that are involved in angiogenic processes, such as the extra domain B of fibronectin, is a promising approach for the diagnosis of solid tumors. The aim of this study was to determine uptake of the (18)F-labeled PET tracers (18)F-fluorocholine (N,N-dimethyl-N-(18)F-fluoromethyl-2-hydroxyethylammonium), (18)F-fluoro-ethyl-l-tyrosine (FET), and (18)F-FDG in C6 gliomas of the rat and to correlate it with uptake of the anti-extra domain B antibody (131)I-SIP(L19) as a marker of neoangiogenesis.. C6 gliomas were orthotopically induced in 17 rats. Uptake of all tracers was measured using quantitative autoradiography, and uptake of (18)F-fluorocholine, (18)F-FET, and (18)F-FDG was correlated with uptake of (131)I-SIP(L19) on a pixelwise basis.. The mean (131)I-SIP(L19), (18)F-fluorocholine, (18)F-FET, and (18)F-FDG standardized uptake values in the tumor and the contralateral normal cortex (in parentheses) were 0.31 +/- 0.22 (not detectable), 2.00 +/- 0.53 (0.49 +/- 0.07), 3.67 +/- 0.36 (1.42 +/- 0.22), and 7.23 +/- 1.22 (3.64 +/- 0.51), respectively. The (131)I-SIP(L19) uptake pattern correlated best with (18)F-fluorocholine uptake (z = 0.80, averaged z-transformed Pearson correlation coefficient) and (18)F-FET uptake (z = 0.79) and least with (18)F-FDG (z = 0.37).. One day after intravenous injection, (131)I-SIP(L19) displayed a very high tumor-to-cortex ratio, which may be used in the diagnostic work-up of brain tumor patients. Of the 3 investigated (18)F tracers, (18)F-fluorocholine and (18)F-FET correlated better with the pattern of (131)I-SIP(L19) uptake than did (18)F-FDG. Whether this means that (18)F-fluorocholine and (18)F-FET are better suited than (18)F-FDG to monitor antiangiogenic therapy should be investigated in future studies.

Topics: Animals; Antibodies; Brain Neoplasms; Cell Line, Tumor; Choline; Fibronectins; Glioma; Male; Neovascularization, Pathologic; Radiopharmaceuticals; Rats; Rats, Wistar; Recombinant Fusion Proteins; Tyrosine

Many low-grade gliomas (World Health Organization grade II) respond to chemotherapy. Cerebral blood flow (CBF) and microvessel density may be critical for drug delivery. We used PET with (18)F-fluoro-ethyl-l-tyrosine (FET) to measure the spatial distribution of the amino acid carrier, which is located at the brain capillaries, and (15)O-H(2)O to measure tumor CBF.. Seventeen patients with low-grade glioma were studied. Region-of-interest (ROI) analysis was used to quantify tumor tracer uptake, which was normalized to cerebellar uptake (tumor-to-cerebellum ratio). "Active" tumor was defined as tumor having a radioactivity concentration that was at least 110% of the cerebellar activity. This threshold provided measures of active tumor volume, global and peak tumor CBF, and (18)F-FET uptake. Trace ROIs were applied to create voxelwise profiles of CBF and (18)F-FET uptake across tumor and brain. Standard MRI sequences were used for spatial correlations.. Fourteen of 17 tumors showed increased global CBF and (18)F-FET uptake. Active tumor volumes ranged between 3 and 270 cm(3) for (18)F-FET and between 1 and 41 cm(3) for CBF. Global (18)F-FET uptake in tumors corresponded to CBF increases (Spearman rank rho = 0.771, P < 0.01). The volumes of increased CBF and (18)F-FET uptake spatially coincided and were also correlated (rho = 0.944, P < 0.01). Trace ROIs showed that irrespective of increased (18)F-FET uptake at the tumor periphery, CBF increases were more confined to the tumor center. Within individual tumors, spatial heterogeneity was present. Particular tumors infiltrating the corpus callosum showed low CBF and (18)F-FET uptake in this tumor region. The patterns observed with PET were not reflected on MRI of the tumors, all of which presented as homogeneous non-gadolinium-enhancing lesions.. Low-grade gliomas are heterogeneous tumors with regard to the distribution of amino acid uptake and CBF. Both are coupled in the tumor center. At the tumor periphery, where tumor infiltration of surrounding brain occurs, CBF may be low irrespective of increased (18)F-FET uptake. An ongoing study is investigating the effect of chemotherapy on these observations.

Topics: Adult; Amino Acid Transport Systems; Brain Neoplasms; Capillaries; Cerebellum; Female; Fluorine Radioisotopes; Glioma; Humans; Male; Microcirculation; Middle Aged; Oxygen Isotopes; Oxygen Radioisotopes; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine; Water

Treatment and prognosis of gliomas depend on their histological tumour grade. The aim of the study was to evaluate the potential of [(18)F]fluoroethyltyrosine (FET) PET for non-invasive tumour grading in untreated patients.. Dynamic FET PET studies were performed in 54 patients who, based on MRI, were estimated to have low grade (LG; n = 20), intermediate (WHO II-III; n = 4) or high grade (HG; n = 30) tumours. For standard evaluation, tumour SUV(max) and the ratio to background (SUV(max)/BG) were calculated (sum image: 20-40 min). For dynamic evaluation, mean SUV values within a 90% isocontour ROI (SUV90) and the SUV90/BG ratios were determined for each time frame to evaluate the course of FET uptake. Results were correlated with histopathological findings from PET-guided stereotactic biopsies.. Histology revealed gliomas in all patients. Using the standard method a statistically significant difference (p = 0.001) was found between LG (n = 20; SUV(max)/BG: 2.16 +/- 0.98) and HG (n = 34; SUV(max)/BG: 3.29 +/- 1.06) gliomas (opt. threshold 2.58: SN71%/SP85%/area under ROC curve [AUC]:0.798), however, with a marked overlap between WHO II to IV tumours. Time activity curves showed slight increase in LG, whereas HG tumours presented with an early peak (10-20 min) followed by a decrease. Dynamic evaluation successfully separated LG from HG gliomas with higher diagnostic accuracy (SN94%/SP100%/AUC:0.967).. Based on the ratio-based method, a statistically significant difference was found between LG and HG gliomas. Due to the interindividual variability, however, no reliable individual grading was possible. In contrast, dynamic evaluation allowed LG and HG gliomas to be differentiated with high diagnostic power and, thus, should supplement the conventional method.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Image Interpretation, Computer-Assisted; Male; Metabolic Clearance Rate; Middle Aged; Neoplasm Staging; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Tyrosine

The positron emission tomography (PET) tracers (18)F-fluoro-ethyl-L: -tyrosine (FET), (18)F-fluorocholine (N,N-dimethyl-N-[(18)F]fluoromethyl-2-hydroxyethylammonium (FCH]) and (18)F-fluoro-2-deoxyglucose (FDG) are used in the diagnosis of brain tumours. The aim of this study was threefold: (a) to assess the uptake of the different tracers in the F98 rat glioma, (b) to evaluate the impact of blood-brain barrier (BBB) disruption and microvessel density (MVD) on tracer uptake and (c) to compare the uptake in the tumours to that in the radiation injuries (induced by proton irradiation of healthy rats) of our previous study.. F98 gliomas were induced in 26 rats. The uptake of FET, FCH and FDG was measured using autoradiography and correlated with histology, disruption of the BBB and MVD.. The mean FET, FCH and FDG standardised uptake values (SUVs) in the tumour and the contralateral normal cortex (in parentheses) were 4.19+/-0.86 (1.32+/-0.26), 2.98+/-0.58 (0.51+/-0.11) and 11.02+/-3.84 (4.76+/-1.77) respectively. MVD was significantly correlated only with FCH uptake. There was a trend towards a negative correlation between the degree of BBB disruption and FCH uptake and a trend towards a positive correlation with FET uptake. The ratio of the uptake in tumours to that in the radiation injuries was 1.97 (FCH), 2.71 (FET) and 2.37 (FDG).. MVD displayed a significant effect only on FCH uptake. The degree of BBB disruption seems to affect the accumulation of FET and FCH, but not FDG. Mean tumour uptake for all tracers was significantly higher than the accumulation in radiation injuries.

Topics: Animals; Blood-Brain Barrier; Brain Injuries; Brain Neoplasms; Cell Line, Tumor; Choline; Fluorodeoxyglucose F18; Glioma; Male; Metabolic Clearance Rate; Radiation Injuries; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Inbred F344; Tyrosine

MRI is commonly used to determine the location and extent of cerebral gliomas. We investigated whether the diagnostic accuracy of MRI could be improved by the additional use of PET with the amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (FET). In a prospective study, PET with FET and MRI was performed in 31 patients with suspected cerebral gliomas. PET and MRIs were co-registered and 52 neuronavigated tissue biopsies were taken from lesions with both abnormal MRI signal and increased FET uptake (match), as well as from areas with abnormal MR signal but normal FET uptake or vice versa (mismatch). Biopsy sites were labelled by intracerebral titanium pellets. The diagnostic performance for the identification of cellular tumour tissue was analysed for either MRI alone or MRI combined with FET PET using alternative free response receiver operating characteristic curves (ROCs). Histologically, 26 biopsy samples corresponded to cellular glioma tissue and 26 to peritumoral brain tissue. The diagnostic performance, as determined by the area under the ROC curve (Az), was Az = 0.80 for MRI alone and Az = 0.98 for the combined MRI and FET PET approach (P < 0.001). MRI yielded a sensitivity of 96% for the detection of tumour tissue but a specificity of only 53%, and combined use of MRI and FET PET yielded a sensitivity of 93% and a specificity of 94%. Combined use of MRI and FET PET in patients with cerebral gliomas significantly improves the identification of cellular glioma tissue and allows definite histological tumour diagnosis. Thus, our findings may have considerable impact on target selection for diagnostic biopsies as well as therapy planning.

Topics: Adolescent; Adult; Aged; Biopsy; Brain Neoplasms; Child; Child, Preschool; Female; Fluorine Radioisotopes; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Prospective Studies; Sensitivity and Specificity; Tyrosine

The purpose of this study was to determine the predictive value of [18F]fluoroethyl-L-tyrosine (FET)-positron emission tomography (PET) and magnetic resonance (MR) spectroscopy for tumor diagnosis in patients with suspected gliomas.. Both FET-PET and MR spectroscopy analyses were performed in 50 consecutive patients with newly diagnosed intracerebral lesions supposed to be diffuse gliomas on contrast-enhanced MR imaging. Lesion/brain ratios of FET uptake greater than 1.6 were considered positive, that is, indicative of tumor. Results of MR spectroscopy were considered positive when N-acetylaspartate (NAA) was decreased in conjunction with an absolute increase of choline (Cho) and an NAA/Cho ratio of 0.7 or less. An FET lesion/brain ratio, an NAA/Cho ratio, and signal abnormalities on MR images were compared with histological findings in neuronavigated biopsy specimens. The FET lesion/brain ratio and the NAA/Cho ratio were identified as significant independent predictors for the histological identification of tumor tissue. The accuracy in distinguishing neoplastic from nonneoplastic tissue could be increased from 68% with the use of MR imaging alone to 97% with MR imaging in conjunction with FET-PET and MR spectroscopy. Sensitivity and specificity for tumor detection were 100 and 81% for MR spectroscopy and 88 and 88% for FET-PET, respectively. Results of histological studies did not reveal tumor tissue in any of the lesions that were negative on FET-PET and MR spectroscopy. In contrast, a tumor diagnosis was made in 97% of the lesions that were positive with both methods.. In patients with intracerebral lesions supposed to be diffuse gliomas on MR imaging, FET-PET and MR spectroscopy analyses markedly improved the diagnostic efficacy of targeted biopsies.

Topics: Adolescent; Adult; Aged; Aspartic Acid; Biopsy; Brain; Brain Neoplasms; Child; Child, Preschool; Choline; Energy Metabolism; Female; Fluorine Radioisotopes; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neuronavigation; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Sensitivity and Specificity; Tyrosine

2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) has been extensively used as positron emission tomography (PET) tracer in clinical tumor imaging. This study compared the pharmacokinetics of two (18)F-labeled amino acid derivatives, O-2-[(18)F]fluoroethyl-l-tyrosine (l-[(18)F]FET) and 4-borono-2-[(18)F]fluoro-l-phenylalanine-fructose (l-[(18)F]FBPA-Fr), to that of [(18)F]FDG in an animal brain tumor model.. A self-modified automated PET tracer synthesizer was used to produce no-carrier-added (nca) l-[(18)F]FET. The cellular uptake, biodistribution, autoradiography and microPET imaging of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG were performed with F98 glioma cell culture and F98 glioma-bearing Fischer344 rats.. The radiochemical purity of l-[(18)F]FET was >98% and the radiochemical yield was 50% in average of 16 runs. The uptake of l-[(18)F]FET and l-[(18)F]FBPA-Fr in the F98 glioma cells increased rapidly for the first 5 min and reached a steady-state level after 10 min of incubation, whereas the cellular uptake of [(18)F]FDG kept increasing during the study period. The biodistribution of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG in the brain tumors was 1.26+/-0.22, 0.86+/-0.08 and 2.77+/-0.44 %ID/g at 60 min postinjection, respectively, while the tumor-to-normal brain ratios of l-[(18)F]FET (3.15) and l-[(18)F]FBPA-Fr (3.44) were higher than that of [(18)F]FDG (1.44). Both microPET images and autoradiograms of l-[(18)F]FET and l-[(18)F]FBPA-Fr exhibited remarkable uptake with high contrast in the brain tumor, whereas [(18)F]FDG showed high uptake in the normal brain and gave blurred brain tumor images.. Both l-[(18)F]FET and l-[(18)F]FBPA-Fr are superior to [(18)F]FDG for the brain tumor imaging as shown in this study with microPET.

Topics: Animals; Boron Compounds; Brain; Brain Neoplasms; Cell Line, Tumor; Disease Models, Animal; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glioma; Glycopeptides; Metabolic Clearance Rate; Molecular Probe Techniques; Organ Specificity; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Tissue Distribution; Tyrosine

Topics: Animals; Autoradiography; Brain; Brain Chemistry; Brain Diseases; Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Proline; Rats; Tyrosine

Differentiation between posttherapy radiation necrosis and recurrent tumor in humans with brain tumor is still a difficult diagnostic task. The new PET tracers (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluorocholine (N,N-dimethyl-N-(18)F-fluoromethyl-2-hydroxyethylammonium [FCH]) have shown promise for improving diagnostic accuracy. This study assessed uptake of these tracers in experimental radiation injury.. In a first model, circumscribed lesions were induced in the cortex of 35 rats using proton irradiation of 150 or 250 Gy. After radiation injury developed, uptake of (18)F-FET, (18)F-FCH, and (18)F-FDG was measured using autoradiography and correlated with histology and disruption of the blood-brain barrier as determined with Evans blue. In a second model, uptake of the tracers was assessed in acute cryolesions, which are characterized by the absence of inflammatory cells.. Mean (18)F-FET, (18)F-FCH, and (18)F-FDG standardized uptake values in the most active part of the radiation lesion and the contralateral normal cortex (in parentheses) were 2.27 +/- 0.46 (1.42 +/- 0.23), 2.52 +/- 0.42 (0.61 +/- 0.12), and 6.21 +/- 1.19 (4.35 +/- 0.47). The degree of uptake of (18)F-FCH and (18)F-FDG correlated with the density of macrophages. In cryolesions, (18)F-FET uptake was similar to that in radiation lesions, and (18)F-FCH uptake was significantly reduced.. Comparison of tracer accumulation in cryolesions and radiation injuries demonstrates that (18)F-FET uptake is most likely due to a disruption of the blood-brain barrier alone, whereas (18)F-FCH is additionally trapped by macrophages. Uptake of both tracers in the radiation injuries is generally lower than the published uptake in tumors, suggesting that (18)F-FET and (18)F-FCH are promising tracers for separating radiation necrosis from tumor recurrence. However, the comparability of our data with the literature is limited by factors such as different species and acquisition protocols and modalities. Thus, more studies are needed to settle this issue. Nevertheless, (18)F-FCH and (18)F-FET seem superior to (18)F-FDG for this purpose.

Topics: Acute Disease; Animals; Brain; Brain Injuries; Brain Neoplasms; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Male; Necrosis; Neoplasm Recurrence, Local; Quaternary Ammonium Compounds; Radiation Injuries, Experimental; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Tyrosine

The whole-body distribution of O-(2-[(18)F]fluoroethyl)- l-tyrosine (FET) was studied in seven patients with brain tumours by positron emission tomography (PET). Based on the IMEDOSE and MIRDOSE procedures, radiation absorbed doses were estimated from whole-body PET scans acquired approximately 70 and 200 min after i.v. injection of 400 MBq FET. After injection of FET, the peak of radioactivity in the blood was observed after 1.5 min, and a plateau of nearly constant radioactivity was reached at 20 min. The whole-body distribution of FET showed the highest activities in the urinary tract. All other organs exhibited only moderate FET uptake (SUV

Topics: Adult; Brain Neoplasms; Female; Fluorine Radioisotopes; Humans; Male; Metabolic Clearance Rate; Middle Aged; Organ Specificity; Radiation Dosage; Radiometry; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution; Tyrosine; Whole-Body Counting

The transport mechanisms of O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) and 2-[(18)F]fluoro-L-tyrosine (FTyr) were compared to those of [(3)H]-Methyl-L-methionine (MET) in F98 rat glioma cells in vitro and by tumor imaging by ex vivo dual tracer autoradiography in F98 rat gliomas. Both, FET and FTyr exhibited similar transport characteristics in F98 glioma cells compared to MET, i.e. mainly a sodium dependent transport similar to system B(0,+) and sodium independent transport via system L. Radioactivity of FET in the acid precipitable fraction was <1% after 120 min incubation time while FTyr and MET exhibited a 15-18% incorporation into proteins. Comparison of FET and FTyr with MET uptake in F98 rat gliomas demonstrated a significant correlation of tumor to brain ratios and a similar intratumoral tracer distribution pattern.

Topics: Animals; Autoradiography; Brain; Brain Neoplasms; Cell Line, Tumor; Glioma; Male; Methionine; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Inbred F344; Tissue Distribution; Tissue Transplantation; Tyrosine

To develop a 18F-labeled amino acid, O-(2-[18F]fluoroethyl) - L-tyrosine(18F-FET), as a positron emission tomography (PET) tracer for imaging cerebral tumors.. 18F-FET was synthesized. Preclinical studies including sterility, endotoxin, and toxicity tests were performed. Two brain tumor cases were studied using 18F-FET and compared with 18F-FDG.. Radiochemical purity of 18F-FET was over 95% which remained stable for 6 hours. The 18F-FET injection was sterile and its endotoxin content accorded with the standards of Chinese Pharmacopoeia. The uptake of 18F-FET in the normal brain tissues was significantly lower than that of the tumor, and the images of the brain tumor were clearer than those of 18F-FDG.. 18F-FET can accumulate in the tumor tissues to give high quality images. It suggests that 18F-FET may be a safe and effective tracer for brain tumor imaging.

Topics: Adult; Animals; Brain Neoplasms; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glioblastoma; Humans; Male; Mice; Middle Aged; Sarcoma 180; Tomography, Emission-Computed; Tyrosine

The aim of the study was to develop a simple 18F-labeled amino acid as a PET tracer for cerebral and peripheral tumors. O-(2-[18F]fluoroethyl)-L-tyrosine (L-[18F]FET) was synthesized and biologically evaluated. Results of the first human PET study are reported.. No carrier added (n.c.a.) and D-[18F]FET were prepared by 18F-fluoroethylation of L- and D-tyrosine in a two-step procedure. Biodistribution studies were performed in mice. The metabolic fate of L-[18F]FET was investigated in plasma, brain, tumor and pancreatic tissue samples using chromatographic procedures. Tumor uptake studies were performed in mammary carcinoma-bearing mice and in mice with the colon carcinoma SW 707. In a human PET study, a 59-y-old man with a recurrent astrocytoma was imaged using n.c.a. L-[18F]FET.. Synthesis of [18F]FET was accomplished in about 50 min with an overall radiochemical yield of 40%. The uptake of L-[18F]FET in the brain of mice reached a level >2% ID/g between 30 and 60 min postinjection. The brain uptake of the D-isomer was negligible, indicating blood-brain barrier penetration by a specific amino acid transport system. L-[18F]FET is not incorporated into proteins. High-performance liquid chromatography (HPLC) analysis of brain, pancreas and tumor homogenates as well as plasma samples of mice at 10, 40 or 60 min postinjection showed only unchanged L-[18F]FET. Activity uptake in the bone did not exceed 2% ID/g at 40 min postinjection. The brain uptake of L-[18F]FET in mice bearing mammary carcinomas and colon carcinomas reached 7.1%+/-1.2% ID/g and 6.4%+/-1.7% ID/g 1h postinjection, respectively. In the first human study, L-[18F]FET-PET allowed a clear delineation of a recurrent astrocytoma. Thirty-five minutes postinjection, the tumor-to-cortex ratio was >2.7. A tumor-to-blood ratio >1.5 was reached at 30 min postinjection and continued to increase. No significant activity accumulation was observed in peripheral organs after approximately 40 min postinjection.. The high in vivo stability of L-[18F]FET, its fast brain and tumor uptake kinetics, its low accumulation in nontumor tissue and its ease of synthesis strongly support further evaluation of L-[18F]FET as an amino acid tracer for cerebral and peripheral tumors.

Topics: Animals; Astrocytoma; Brain Neoplasms; Chromatography, High Pressure Liquid; Colonic Neoplasms; Female; Humans; Male; Mammary Neoplasms, Experimental; Mice; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Transplantation; Tissue Distribution; Tomography, Emission-Computed; Transplantation, Heterologous; Tyrosine