18f-fluoroethyl-l-tyrosine and Glioblastoma

Gliomas are the most common primary tumors involving the central nervous system. They can manifest with diverse and non-specific general and neurological symptoms. The diagnostic gold standard is cerebral magnetic resonance imaging and subsequent histological confirmation of the diagnosis. Steroids, especially dexamethasone, are used in case of focal symptoms and of symptoms caused by increased intracranial pressure, and antiepileptic drugs are used to manage epileptic seizures. Non-enzyme-inducing antiepileptic drugs are preferable. Glioma patients have an inherently elevated thromboembolic risk, and therapeutic anticoagulation is indicated following a thromboembolic event. Surgery, radiotherapy and systemic therapy are used as tumor-specific therapy modalities in gliomas. Molecular markers play an increasing role in the prognosis and selection of therapy in daily oncological routine.

Topics: Anticoagulants; Anticonvulsants; Brain Neoplasms; Combined Modality Therapy; Dexamethasone; Diagnosis, Differential; Glioblastoma; Glioma; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Oligodendroglioma; Positron-Emission Tomography; Tyrosine

To explore a prognostic or predictive role of MRI and O-(2-. Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this. Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm. Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent

Topics: Aged; Aged, 80 and over; Bevacizumab; Brain; Brain Neoplasms; Chemoradiotherapy; Female; Glioblastoma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Progression-Free Survival; Radiopharmaceuticals; Tyrosine

After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastoma patients at first progression (age range, 33-75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8-10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates.. Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P < 0.05). The absolute MTV at follow-up enabled the most significant OS prediction (sensitivity, 85%; specificity, 88%; P = 0.001). Patients with an absolute MTV below 5 ml at follow-up survived significantly longer (12 vs. 6 months, P < 0.001), whereas early responders defined by RANO criteria lived only insignificantly longer (9 vs. 6 months; P = 0.072). The absolute MTV at follow-up remained significant in the multivariate survival analysis (P = 0.006).. FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.

Topics: Adult; Aged; Bevacizumab; Disease Progression; Drug Interactions; Female; Glioblastoma; Humans; Lomustine; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Survival Analysis; Treatment Outcome; Tyrosine

In MRI of patients with recurrent glioblastoma, bevacizumab-induced normalization of tumor vascularity can be difficult to differentiate from antitumor effects. The aim of this study was to assess the utility of. MRI and FET PET were performed before and after administration of two doses of bevacizumab to 11 patients with recurrent glioblastoma. The ratio between normalized FET uptake at follow-up and baseline of the entire (volume of T2 FLAIR abnormality) and enhancing tumor were assessed for prediction of progression-free survival (PFS) and overall survival (OS). Voxel-wise Spearman correlation between normalized FET uptake and contrast-enhanced T1 signal intensity was assessed and tested as a predictor of PFS and OS.. Mean Spearman correlation between FET uptake and contrast-enhanced T1 signal intensity before therapy was 0.65 and after therapy was 0.61 (p = 0.256). The median PFS after initiation of bevacizumab therapy was 111 days, and the OS was 223 days. A post-treatment to pretreatment PET uptake ratio (mean and 90th percentile) greater than 0.7 for both entire and enhancing tumor was associated with lower PFS and OS (p < 0.001-0.049). The increase in correlation between PET uptake and contrast-enhanced T1 intensity after treatment was associated with lower PFS (p < 0.001) and OS (p = 0.049).. There is only a moderate correlation between FET PET uptake and contrast-enhanced T1 signal intensity. High posttreatment-to-pretreatment FET PET uptake ratio and increase in correlation between PET uptake and contrast-enhanced T1 signal intensity after bevacizumab treatment are associated with poor PFS and OS.

Topics: Angiogenesis Inhibitors; Bevacizumab; Brain Neoplasms; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Predictive Value of Tests; Tyrosine

The value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET)-radiomics in the outcome assessment of patients with recurrent glioblastoma (rGBM) has not been evaluated until now. The aim of this study was to evaluate whether a prognostic model based on FET-PET radiomics features (RF) is feasible and can identify rGBM patients that would most benefit from re-irradiation.. We prospectively recruited rGBM patients who underwent FET-PET before re-irradiation (GLIAA-Pilot trial, DRKS00000633). Tumor volume was delineated using a semi-automatic method with a threshold of 1.8 times the standardized-uptake-value of the background. 135 FET-RF (histogram parameters, shape and texture features) were extracted. The analysis involved the characterization of tumor and non-tumor tissue with FET-RF and the evaluation of the prognostic value of FET-RF for time-to-progression (TTP), overall survival (OS) and recurrence location (RL).. Thirty-two rGBM patients constituted our cohort. FET-RF discriminated significantly between tumor and non-tumor. The texture feature Small-Zone-Low-Gray-Level-Emphasis (SZLGE) showed the best performance for the prediction of TTP (p = 0.001, satisfying Bonferroni-multiple-test significance level). Additionally, two radiomics signatures could predict TTP (TTP-radiomics-signature, p = 0.001) and OS (OS-radiomics-signature, p = 0.038). SZLGE and the TTP-radiomics-signature additionally predicted RL. Specifically, high values for TTP-radiomics-signature and for SZLGE indicated not only earlier progression, but also a RL within the initial FET-PET active volume.. Our findings suggest that FET-PET radiomics could contribute to the prognostic assessment and selection of rGBM-patients benefiting from re-irradiation. Trial registration DRKS00000633. Registered on 8th of December in 2010. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00000633 .

Topics: Adult; Aged; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Prospective Studies; Radiopharmaceuticals; Re-Irradiation; Treatment Outcome; Tyrosine

Glioma stem cells (GSCs) are the source of tumor recurrence in glioblastoma and are capable of whole tumor regeneration once the treatment has concluded. Compelling evidence from the last decade suggests that GSC may arise from neural stem cells residing in the adult subventricular zone (SVZ). We report the findings of an 18F-FET PET/CT showing pathological uptake in SVZ with a tumor-background ratio of greater than 1.6, giving evidence for glioblastoma recurrence. This case highlights the particular attention to be paid to the SVZ given the possible development of GSC.

Topics: Adult; Brain Neoplasms; Female; Glioblastoma; Humans; Lateral Ventricles; Positron Emission Tomography Computed Tomography; Recurrence; Tyrosine

Diagnostic accuracy in previous studies of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in patients with suspected recurrent glioma may be influenced by prolonged dynamic PET acquisitions, heterogeneous populations, different non-standard-of-care therapies, and PET scans performed at different time points post radiotherapy. We investigated the diagnostic accuracy of a 20-minute 18F-FET PET scan in MRI-suspected recurrent glioblastoma 6 months after standard radiotherapy and its ability to prognosticate overall survival (OS).. In total, 146 glioblastoma patients with 168 18F-FET PET scans were reviewed retrospectively. Patients with MRI responses to bevacizumab or undergoing re-irradiation or immunotherapy after 18F-FET PET were excluded. Maximum and mean tumor-to-background ratios (TBRmax, TBRmean) and biological tumor volume (BTV) were recorded and verified by histopathology or clinical/radiological follow-up. Thresholds of 18F-FET parameters were determined by receiver operating characteristic (ROC) analysis. Prognostic factors were investigated in Cox proportional hazards models.. Surgery was performed after 104 18F-FET PET scans, while clinical/radiological surveillance was used following 64, identifying 152 glioblastoma recurrences and 16 posttreatment changes. ROC analysis yielded thresholds of 2.0 for TBRmax, 1.8 for TBRmean, and 0.55 cm3 for BTV in differentiating recurrent glioblastoma from posttreatment changes with the best performance of TBRmax (sensitivity 99%, specificity 94%; P < 0.0001) followed by BTV (sensitivity 98%, specificity 94%; P < 0.0001). Using these thresholds, 166 18F-FET PET scans were correctly classified. Increasing BTV was associated with shorter OS (P < 0.0001).. A 20-minute 18F-FET PET scan is a powerful tool to distinguish posttreatment changes from recurrent glioblastoma 6-month postradiotherapy, and predicts OS.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Chemoradiotherapy; Combined Modality Therapy; Female; Follow-Up Studies; Glioblastoma; Humans; Immunotherapy; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Survival Rate; Tyrosine; Young Adult

Areas of contrast enhancement (CE) on MRI are usually the target for resection or radiotherapy target volume definition in glioblastomas. However, the solid tumour mass may extend beyond areas of CE. Amino acid PET can detect parts of the tumour that show no CE. We systematically investigated tumour volumes delineated by amino acid PET and MRI in patients with newly diagnosed, untreated glioblastoma.. Preoperatively, 50 patients with neuropathologically confirmed glioblastoma underwent O-(2-[. In 43 patients (86%), the FET tumour volume was significantly larger than the CE volume (21.5 ± 14.3 mL vs. 9.4 ± 11.3 mL; P < 0.001). Forty patients (80%) showed both increased uptake of FET and CE. In these 40 patients, the spatial similarity between FET uptake and CE was low (mean DSC 0.39 ± 0.21, mean JSC 0.26 ± 0.16). Ten patients (20%) showed no CE, and one of these patients showed no FET uptake. In five patients (10%), increased FET uptake was present outside areas of FLAIR hyperintensity.. Our results show that the metabolically active tumour volume delineated by FET PET is significantly larger than tumour volume delineated by CE. Furthermore, the results strongly suggest that the information derived from both imaging modalities should be integrated into the management of patients with newly diagnosed glioblastoma.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioblastoma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Tumor Burden; Tyrosine

The use of O-(2-[

Topics: Animals; Apoptosis; Cell Proliferation; Female; Glioblastoma; Humans; Large Neutral Amino Acid-Transporter 1; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Tumor Cells, Cultured; Tyrosine; Xenograft Model Antitumor Assays

Glioblastoma (GBM) is a highly invasive brain tumor, whose cells infiltrate surrounding normal brain tissue beyond the lesion outlines visible in the current medical scans. These infiltrative cells are treated mainly by radiotherapy. Existing radiotherapy plans for brain tumors derive from population studies and scarcely account for patient-specific conditions. Here, we provide a Bayesian machine learning framework for the rational design of improved, personalized radiotherapy plans using mathematical modeling and patient multimodal medical scans. Our method, for the first time, integrates complementary information from high-resolution MRI scans and highly specific FET-PET metabolic maps to infer tumor cell density in GBM patients. The Bayesian framework quantifies imaging and modeling uncertainties and predicts patient-specific tumor cell density with credible intervals. The proposed methodology relies only on data acquired at a single time point and, thus, is applicable to standard clinical settings. An initial clinical population study shows that the radiotherapy plans generated from the inferred tumor cell infiltration maps spare more healthy tissue thereby reducing radiation toxicity while yielding comparable accuracy with standard radiotherapy protocols. Moreover, the inferred regions of high tumor cell densities coincide with the tumor radioresistant areas, providing guidance for personalized dose-escalation. The proposed integration of multimodal scans and mathematical modeling provides a robust, non-invasive tool to assist personalized radiotherapy design.

Topics: Bayes Theorem; Brain; Brain Neoplasms; Glioblastoma; Humans; Multimodal Imaging; Positron-Emission Tomography; Precision Medicine; Radiotherapy Planning, Computer-Assisted; Tyrosine

Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT. In this project we investigated the feasibility and treatment response of subvolume boosting to a PET-defined tumor part.. F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (T1w) MRI. A dose of 20 Gy (5 × 5 mm. When comparing the dose volume histograms, a significant difference was found exclusively between the D. In this study we showed the feasibility of PET guided subvolume boosting of F98 glioblastoma in rats. No evidence was found for a beneficial effect regarding tumor response. However, improvements for dose targeting in rodents and studies investigating new targeted drugs for GB treatment are mandatory.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Disease Models, Animal; Feasibility Studies; Female; Glioblastoma; Nitroimidazoles; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Image-Guided; Rats, Inbred F344; Treatment Outcome; Tumor Burden; Tyrosine

The value of early postoperative 18F-FET-PET in patients with glioblastoma (GBM) is unclear. Five-aminolevulinic acid (5-ALA) is used for fluorescence-guided resections in these patients and previous data suggest that fluorescence and 18F-FET-PET both demarcate larger tumor volumes than gadolinium enhanced magnet resonance imaging (MRI).. To correlate fluorescence with enhancing volumes on postoperative MRI and 18F-FET-PET tumor volumes, and determine the value of postoperative 18F-FET-PET for predicting survival through observational study.. GBM patients underwent fluorescence-guided resection after administration of 5-ALA followed by early postoperative MRI and 18F-FET-PET for determination of residual tissue volumes. All patients were treated with standard temozolomide radiochemotherapy and monitored for progression-free and overall survival (PFS, OS).. A total of 31 patients were included. For functional reasons, residual 5-ALA derived fluorescent tissue was left unresected in 18 patients with a median 18F-FET-PET volume of 17.82 cm3 (interquartile range 6.50-29.19). In patients without residual fluorescence, median 18F-FET-PET volume was 1.20 cm3 (interquartile range 0.87-5.50) and complete resection of gadolinium enhancing tumor was observed in 100% of patients. A 18F-FET-PET volume of above 4.3 cm3 was associated with worse OS (logrank P-value ≤ .05), also in patients with no residual contrast enhancing tumor on MRI. More patients in whom fluorescencing tissue had been removed completely had postoperative 18F-FET-PET tumor volumes below 4.3 cm3.. Postoperative 18F-FET-PET volumes predict OS and PFS. Resection of 5-ALA derived fluorescence beyond gadolinium enhancing tumor tissue leads to lower postoperative 18F-FET-PET tumor volumes and improved OS and PFS without additional deficits.

Topics: Aminolevulinic Acid; Brain Neoplasms; Gadolinium; Glioblastoma; Humans; Optical Imaging; Positron-Emission Tomography; Tyrosine

In a subset of glioblastoma (GBM) patients, the differentiation between tumor progression and tumor pseudoprogression (PsP) is challenging. This case describes a male patient suffering from isocitrate dehydrogenase 1 (IDH1) mutant GBM who demonstrated an increasing contrast-enhancing (CE) lesion on a cranial magnetic resonance imaging (cMRI) scan 8 months after radiochemotherapy. In accordance with the response assessment in neuro-oncology (RANO) criteria, the cMRI lesion was classified as recurrent tumor, although

Topics: Aged; Brain Neoplasms; Chemoradiotherapy; Disease Progression; Glioblastoma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tyrosine

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. We studied the uptake kinetics of [

Topics: Carbon; Cell Line, Tumor; Choline; Diagnosis, Differential; Glioblastoma; Humans; Ions; Neoplasm Metastasis; Photons; Tyrosine

(S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.. For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.. In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.. 18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.. ClinicalTrials.gov NCT01186601.

Topics: Adult; Aged; Animals; Brain Neoplasms; Case-Control Studies; Cell Line, Tumor; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Glioblastoma; Glutamic Acid; Heterografts; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Tomography, X-Ray Computed; Tyrosine

Complete resection of contrast-enhancing tumor is an important prognostic factor in glioblastoma therapy. The current clinical standard for control of resection is magnetic resonance imaging (MRI). (18)F-Fluoroethyl-l-thyrosine (FET) is a positron emission tomography (PET) radiopharmaceutical applicable for widespread use because of its long half-life radionuclide. We assessed the sensitivity of postoperative MRI versus FET-PET to detect residual tumor and the impact of the time interval between resection and FET-PET.. MRI and FET-PET were performed preoperatively and postoperatively in 62 patients undergoing 63 operations. FET-PET was performed in 43 cases within 72 hours after resection and in 20 cases >72 hours after resection. Detection and measurement of volume of residual tumors were compared. Correlations between residual tumor detection and timing of PET after resection and recurrence were examined.. Complete resection was confirmed by both imaging modalities in 44% of cases, and residual tumor was detected consistently in 37% of cases. FET-PET detected residual tumor in 14% of cases in which MRI showed no residual tumor. MRI showed residual tumors in 5% of cases that were not identified by PET. Average PET-based residual tumor volume was higher than MRI-based volume (3.99 cm(3) vs. 1.59 cm(3)). Detection of and difference in volume of residual tumor were not correlated with timing of PET after resection or recurrence status.. Postoperative FET-PET revealed residual tumor with higher sensitivity than MRI and showed larger tumor volumes. In this series, performing PET >72 hours after resection did not influence the results of PET. We recommend FET-PET as a helpful adjunct in addition to MRI for postoperative assessment of residual tumor.

Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Neoplasms; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm, Residual; Positron-Emission Tomography; Postoperative Period; Preoperative Period; Radiopharmaceuticals; Sensitivity and Specificity; Time Factors; Tyrosine

The radiolabeled amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) and thymidine analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, comparative studies are scarce. The aim of this study therefore was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts.. Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow treatment response. Tracer uptake of FLT and FET was quantified using maximum standardized uptake (SUVmax) values and tumor-to-background ratios (TBRs). Survival, the Ki67 proliferation index and micro-vessel density (MVD) were evaluated.. In contrast to FLT TBRs, FET TBRs were significantly lower as early as one week after treatment initiation in the anti-VEGF group as compared to the control group. Following two weeks of treatment, both FLT and FET TBRs were significantly lower in the anti-VEGF group. In contrast, no significant difference between the treatment groups was detected using BLI. Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time.. FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET. Advances in knowledge and implications for patient care FET PET appears to be an early predictor of anti-VEGF efficacy. Confirmation of these results in clinical studies is needed.

Topics: Animals; Bevacizumab; Brain Neoplasms; Cell Transformation, Neoplastic; Dideoxynucleosides; Female; Glioblastoma; HEK293 Cells; Humans; Mice; Microvessels; Positron-Emission Tomography; Survival Analysis; Tyrosine; Vascular Endothelial Growth Factor A

Resistance to bevacizumab (BEV) in glioblastoma is believed to occur via activation of molecular networks including the mTOR/PI3K pathway. Using an MR/PET molecular imaging biomarker approach, we investigated the response to combining BEV with the mTOR/PI3K inhibitor BEZ235.. Tumours were established by orthotopically implanting U87MG-luc2 cells in mice. Animals were treated with BEZ235 and/or BEV, and imaged using diffusion-weighted-MRI, T2-weighted and T2*-weighted before and after administration of superparamagnetic iron oxide contrast agent. Maps for changes in relaxation rates (ΔR2, ΔR2* and apparent diffusion coefficient) were calculated. Vessel size index and microvessel density index were derived. 3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) PET and O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) PET were further performed and tumour endothelium/proliferation markers assessed by immunohistochemistry.. Treatment with BEV resulted in a pronounced decrease in tumour volume (T2-weighted MRI). No additive effect on tumour volume was observed with the BEV/BEZ235 combination compared with BEV monotherapy. The Ki67 proliferation index and [(18)F]FLT uptake studies were used to support the observations. Using ΔR2* and ΔR2 values, respectively, the BEV/BEZ235 combination significantly reduced tumour microvessel volume in comparison to BEV alone. Decreased microvessel density index was further observed in animals treated with the combination, supported by von Willebrand factor (vWF) immunohistochemistry. [(18)F]FET uptake was decreased following treatment with BEV alone, but was not further reduced following treatment with the combination. vWF immunohistochemistry analysis showed that the mean tumour vessel size was increased in all cohorts.. Assessing MR imaging biomarker parameters together with [(18)F]FET and [(18)F]FLT PET provided information on mechanism of action of the drug combination and clues as to potential clinical responses. Following translation to clinical use, treatment with a BEV/BEZ235 combination could reduce peritumoral oedema obviating the requirement for steroids. The use of hypothesis-driven molecular imaging studies facilitates the preclinical evaluation of drug response. Studies of this kind may more accurately predict the clinical potential of the BEV/BEZ235 combination regimen as a novel therapeutic approach in oncology.

Topics: Animals; Bevacizumab; Biological Transport; Biomarkers, Tumor; Cell Line, Tumor; Drug Interactions; Female; Glioblastoma; Humans; Imidazoles; Magnetic Resonance Imaging; Mice; Microvessels; Multimodal Imaging; Phosphoinositide-3 Kinase Inhibitors; Positron-Emission Tomography; Protein Kinase Inhibitors; Quinolines; TOR Serine-Threonine Kinases; Tumor Burden; Tyrosine; Xenograft Model Antitumor Assays

The diagnostic accuracy of magnetic resonance imaging (MRI) for glioblastoma multiforme (GBM) is suboptimal. We analysed pre-treatment MRI- and dual time-point 18F-fluoroethylthyrosine-PET (FET-PET)-based target volumes and GBM recurrence patterns following radiotherapy with temozolomide.. Thirty-four patients with primary GBM were treated according to MRI-based treatment volumes (GTVRM). Patients underwent dual time-point FET-PET scans prior to treatment, and biological tumour volumes (GTVPET) were contoured but not used for target definition. Progressions were classified based on location of primary GTVs. Volume and uniformity of MRI- vs. FET-PET/CT-derived GTVs and progression patterns assessed by MRI were analysed.. FET-based GTVs measured 10min after radionuclide injection (a.r.i.; median 37.3cm(3)) were larger than GTVs measured 60min a.r.i. (median 27.7cm(3)). GTVPET volumes were significantly larger than corresponding MRI-based GTVs. MRI and PET concordance for the identification of glioblastoma GTVs was poor (mean uniformity index 0.4). 74% of failures were inside primary GTVPET volumes, with no solitary progressions inside the MRI-defined margin +20mm but outside the GTVPET detected.. The size and geometry of GTVs differed in the majority of patients. The GTVPET volume depends on time after radionuclide injection. FET-PET better defined failure site than MRI alone.

Topics: Adolescent; Adult; Aged; Disease Progression; Female; Follow-Up Studies; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prognosis; Prospective Studies; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Tumor Burden; Tyrosine; Young Adult

Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results.. Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed.. The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN.. Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN.

Topics: Animals; Brain; Cell Line, Tumor; Choline; Diagnosis, Differential; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Glioblastoma; Humans; Kinetics; Necrosis; Neoplasm Grading; Positron-Emission Tomography; Radiation Injuries; Radiopharmaceuticals; Rats, Inbred F344; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

Discrimination between (high-grade) brain tumor recurrence and radiation necrosis (RN) remains a diagnostic challenge because both entities have similar imaging characteristics on conventional magnetic resonance imaging (MRI). Metabolic imaging, such as positron emission tomography (PET) could overcome this diagnostic dilemma. In this study, we investigated the potential of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG), O-(2-[(18)F]-fluoroethyl)-L-tyrosine ((18)F-FET), and [(18)F]-Fluoromethyl-dimethyl-2-hydroxyethylammonium ((18)F-fluoromethylcholine, (18)F-FCho) PET in discriminating high-grade tumor from RN.. We developed a glioblastoma (GB) rat model by inoculating F98 GB cells into the right frontal region. Induction of RN was achieved by irradiating the right frontal region with 60 Gy using three arcs with a beam aperture of 3×3 mm (n=3). Dynamic PET imaging with (18)F-FDG, (18)F-FET, and (18)F-FCho, as well as (18)F-FDG PET at a delayed time interval (240 min postinjection), was acquired.. MRI revealed contrast-enhancing tumors at 15 days after inoculation (n=4) and contrast-enhancing RN lesions 5-6 months postirradiation (n=3). On (18)F-FDG PET, the mean lesion-to-normal ratio (LNRmean) was significantly higher in GB than in RN (p=0.034). The difference in the LNRmean between tumors and RN was higher on the late (18)F-FDG PET images than on the PET images reconstructed from the last time frame of the dynamic acquisition (this is at a conventional time interval). LNRs obtained from (18)F-FCho PET were not significantly different between GB and RN (p=1.000). On (18)F-FET PET, the LNRmean was significantly higher in GB compared to RN (p=0.034).. Unlike (18)F-FCho, (18)F-FDG and (18)F-FET PET were effective in discriminating GB from RN. Interestingly, in the case of (18)F-FDG, delayed PET seems particularly useful.. Our results suggest that (delayed) (18)F-FDG and (18)F-FET PET can be used to discriminate GB (recurrence) from RN. Confirmation of these results in clinical studies is needed.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Choline; Diagnosis, Differential; Female; Fluorodeoxyglucose F18; Glioblastoma; Necrosis; Neoplasm Grading; Positron-Emission Tomography; Radiation Injuries; Radioactive Tracers; Radiopharmaceuticals; Rats; Recurrence; Tyrosine

The aim of this prospective longitudinal study was to identify static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine PET ((18)FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM).. Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). (18)FET-PET evaluation using static and dynamic analysis was done before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models.. Biological tumor volume before RCx (BTV(preRCx)) was the most important (18)FET-PET-derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller BTV(preRCx) had significantly longer progression-free and overall survival (OS). (18)FET time-activity curves (TACs) before treatment and their changes after RCx were also related to outcome; patients with initially increasing TACs experienced longer OS.. BTV(preRCx) and TAC represent important (18)FET-PET-derived imaging biomarkers in GBM. Increasing TACs are associated with prolonged OS. The BTV(preRCx) is a strong prognostic factor for progression-free survival and OS independent of the mode of surgery. Our data furthermore suggest that patients harboring resectable GBM might benefit from maximal PET-guided tumor resection.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain; Brain Neoplasms; Chemoradiotherapy; Combined Modality Therapy; Dacarbazine; Disease-Free Survival; Female; Glioblastoma; Humans; Longitudinal Studies; Male; Microsurgery; Middle Aged; Neurosurgical Procedures; Positron-Emission Tomography; Prospective Studies; Temozolomide; Treatment Outcome; Tumor Burden; Tyrosine

Conflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of 18F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of 18F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts.. Mice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), 18F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours.. Anti-VEGF monotherapy increased survival and decreased 18F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. 18F-FET SUV max tumour-to-brain (T/B) ratio was significantly lower after one week (114 ± 6%, n = 11 vs. 143 ± 8%, n = 13; p = 0.02) and two weeks of treatment (116 ± 12%, n = 8 vs. 190 ± 24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours.. 18F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of 18F-FET PET for response evaluation in future studies.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Line, Tumor; Cell Transformation, Neoplastic; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Magnetic Resonance Imaging; Membrane Proteins; Mice; Microvessels; Multimodal Imaging; Optical Imaging; Positron-Emission Tomography; RNA, Messenger; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome; Tyrosine; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

Here we compare translocator protein (TSPO) imaging using 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide SPECT ((123)I-CLINDE) and amino acid transport imaging using O-(2-(18)F-fluoroethyl)-l-tyrosine PET ((18)F-FET) and investigate whether (123)I-CLINDE is superior to (18)F-FET in predicting progression of glioblastoma multiforme (GBM) at follow-up.. Three patients with World Health Organization grade IV GBM were scanned with (123)I-CLINDE SPECT, (18)F-FET PET, and gadolinium-enhanced MR imaging. Molecular imaging data were compared with follow-up gadolinium-enhanced MR images or contrast-enhanced CT scans.. The percentage overlap between volumes of interest (VOIs) of increased (18)F-FET uptake and (123)I-CLINDE binding was variable (12%-42%). The percentage overlap of MR imaging baseline VOIs was greater for (18)F-FET (79%-93%) than (123)I-CLINDE (15%-30%). In contrast, VOIs of increased contrast enhancement at follow-up compared with baseline overlapped to a greater extent with baseline (123)I-CLINDE VOIs than (18)F-FET VOIs (21% vs. 8% and 72% vs. 55%).. Our preliminary results suggest that TSPO brain imaging in GBM may be a useful tool for predicting tumor progression at follow-up and may be less susceptible to changes in blood-brain barrier permeability than (18)F-FET. Larger studies are warranted to test the clinical potential of TSPO imaging in GBM, including presurgical planning and radiotherapy.

Topics: Aged; Biomarkers, Tumor; Brain Neoplasms; Bridged Bicyclo Compounds, Heterocyclic; Female; Fluorodeoxyglucose F18; Gadolinium; Glioblastoma; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Molecular Imaging; Radiopharmaceuticals; Receptors, GABA; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution; Tomography, Emission-Computed; Tyrosine

Both (18)F-fluorodihydroxyphenylalanine ((18)F-DOPA) and (18)F-fluoroethyltyrosine ((18)F-FET) have already been used successfully for imaging of brain tumors. The aim of this study was to evaluate differences between these 2 promising tracers to determine the consequences for imaging protocols and the interpretation of findings.. Forty minutes of dynamic PET imaging were performed on 2 consecutive days with both (18)F-DOPA and (18)F-FET in patients with recurrent low-grade astrocytoma (n = 8) or high-grade glioblastoma (n = 8). Time-activity-curves (TACs), standardized uptake values (SUVs) and compartment modeling of both tracers were analyzed, respectively.. The TAC of DOPA-PET peaked at 8 minutes p.i. with SUV 5.23 in high-grade gliomas and 10 minutes p.i. with SUV 4.92 in low-grade gliomas. FET-PET peaked at 9 minutes p.i. with SUV 3.17 in high-grade gliomas and 40 minutes p.i. with SUV 3.24 in low-grade gliomas. Neglecting the specific uptake of DOPA into the striatum, the tumor-to-brain and tumor-to-blood ratios were higher for DOPA-PET. Kinetic modeling demonstrated a high flow constant k1 (mL/ccm/min), representing cellular internalization through AS-transporters, for DOPA in both high-grade (k1 = 0.59) and low-grade (k1 = 0.55) tumors, while lower absolute values and a relevant dependency from tumor-grading (high-grade k1 = 0.43; low-grade k1 = 0.33) were observed with FET.. DOPA-PET demonstrates superior contrast ratios for lesions outside the striatum, but SUVs do not correlate with grading. FET-PET can provide additional information on tumor grading and benefits from lower striatal uptake but presents lower contrast ratios and requires prolonged imaging if histology is not available in advance due to a more variable time-to-peak.

Topics: Astrocytoma; Brain Neoplasms; Dihydroxyphenylalanine; Glioblastoma; Humans; Neoplasm Recurrence, Local; Positron-Emission Tomography; Tyrosine

Brain tumor imaging is challenging. Although 18F-FET PET is widely used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in xenograft has not been assessed to date. The aim of this study therefore was to evaluate the performance of in vivo 18F-FET MicroPET in detecting a treatment response in xenografts. In addition, the correlations between the 18F-FET tumor accumulation and the gene expression of Ki67 and the amino acid transporters LAT1 and LAT2 were investigated. Furthermore, Ki67, LAT1 and LAT2 gene expression in xenograft and archival patient tumors was compared.. Human GBM cells were injected orthotopically in nude mice and 18F-FET uptake was followed by weekly MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or saline weekly. After two weeks of treatment the brain tumors were isolated and quantitative polymerase chain reaction were performed on the xenograft tumors and in parallel on archival patient tumor specimens.. The relative tumor-to-brain (T/B) ratio of SUV max was significantly lower after one week (123 ± 6%, n = 7 vs. 147 ± 6%, n = 7; p = 0.018) and after two weeks (142 ± 8%, n = 5 vs. 204 ± 27%, n = 4; p = 0.047) in the CPT-11 group compared with the control group. Strong negative correlations between SUV max T/B ratio and LAT1 (r = -0.62, p = 0.04) and LAT2 (r = -0.67, p = 0.02) were observed. In addition, a strong positive correlation between LAT1 and Ki67 was detected in xenografts. Furthermore, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression of LAT2 were observed in patient specimens compared to xenografts.. 18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM xenografts. The strong negative correlation between SUV max T/B ratio and LAT1/LAT2 indicates an export transport function. We suggest that 18F-FET PET may be used for detection of early treatment response in patients.

Topics: Animals; Antineoplastic Agents, Phytogenic; Brain; Brain Neoplasms; Camptothecin; Cell Line, Tumor; Female; Glioblastoma; Heterografts; Humans; Irinotecan; Mice, Nude; Neuroimaging; Positron-Emission Tomography; Tyrosine

Treatment of recurrent glioblastoma (rGBM) remains an unsolved clinical problem. Reirradiation (re-RT) can be used to treat some patients with rGBM, but as a monotherapy it has only limited efficacy. Chloroquine (CQ) is an anti-malaria and immunomodulatory drug that may inhibit autophagy and increase the radiosensitivity of GBM.. Between January 2012 and August 2013, we treated five patients with histologically confirmed rGBM with re-RT and 250 mg CQ daily.. Treatment was very well tolerated; no CQ-related toxicity was observed. At the first follow-up 2 months after finishing re-RT, two patients achieved partial response (PR), one patient stable disease (SD), and one patient progressive disease (PD). One patient with reirradiated surgical cavity did not show any sign of PD.. In this case series, we observed encouraging responses to CQ and re-RT. We plan to conduct a CQ dose escalation study combined with re-RT.

Topics: Adult; Brain Neoplasms; Chloroquine; Feasibility Studies; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pilot Projects; Positron-Emission Tomography; Radiation-Sensitizing Agents; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Image-Guided; Treatment Outcome; Tyrosine

The assessment of treatment response in glioblastoma is difficult with MRI because reactive blood-brain barrier alterations with contrast enhancement can mimic tumor progression. In this study, we investigated the predictive value of PET using O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET PET) during treatment.. In a prospective study, 25 patients with glioblastoma were investigated by MRI and (18)F-FET PET after surgery (MRI-/FET-1), early (7-10 d) after completion of radiochemotherapy with temozolomide (RCX) (MRI-/FET-2), and 6-8 wk later (MRI-/FET-3). Maximum and mean tumor-to-brain ratios (TBR(max) and TBR(mean), respectively) were determined by region-of-interest analyses. Furthermore, gadolinium contrast-enhancement volumes on MRI (Gd-volume) and tumor volumes in (18)F-FET PET images with a tumor-to-brain ratio greater than 1.6 (T(vol 1.6)) were calculated using threshold-based volume-of-interest analyses. The patients were grouped into responders and nonresponders according to the changes of these parameters at different cutoffs, and the influence on progression-free survival and overall survival was tested using univariate and multivariate survival analyses and by receiver-operating-characteristic analyses.. Early after completion of RCX, a decrease of both TBR(max) and TBR(mean) was a highly significant and independent statistical predictor for progression-free survival and overall survival. Receiver-operating-characteristic analysis showed that a decrease of the TBR(max) between FET-1 and FET-2 of more than 20% predicted favorable survival [corrected], with a sensitivity of 83% and a specificity of 67% (area under the curve, 0.75). Six to eight weeks later, the predictive value of TBR(max) and TBR(mean) was less significant, but an association between a decrease of T(vol 1.6) and PFS was noted. In contrast, Gd-volume changes had no significant predictive value for survival.. In contrast to Gd-volumes on MRI, changes in (18)F-FET PET may be a valuable parameter to assess treatment response in glioblastoma and to predict survival time.

Topics: Adult; Aged; Brain Neoplasms; Chemoradiotherapy; Contrast Media; Disease Progression; Disease-Free Survival; Female; Gadolinium; Glioblastoma; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Positron-Emission Tomography; Prognosis; Proportional Hazards Models; Prospective Studies; Radiopharmaceuticals; Survival Analysis; Treatment Outcome; Tyrosine

The aim of the present study was to evaluate factors predicting the recurrence pattern determined by [(18)F]FET-PET imaging in patients with newly diagnosed glioblastoma after combined radio-chemotherapy treated according to the EORTC/NCIC trial.. Seventy-nine patients with newly diagnosed GBM treated with radiotherapy plus temozolomide (75 mg/m(2)/d) followed by adjuvant cyclic (5/28 days) temozolomide (150-200 mg/m(2)) were retrospectively analysed. Recurrence patterns were assessed by means of positron-emission-tomography with [(18)F]FET and additional MRI; in 54 patients MGMT methylation status was evaluated.. Whilst 49.4% of the patients had an in-field recurrence, 12.6% an ex-field recurrence and 3.8% a recurrence at the field margin, 34.2% of the patients did not relapse during follow-up (median 595 days). Considering all patients included in this study, 41.5% (12/29) of the MGMT methylated population had no relapse, 37.9% (11/29) had an in-field-recurrence and 20.7% (6/29) an ex-field/marginal recurrence, whilst 28.0% (7/25) of the MGMT unmethylated population had no relapse, 64.0% (16/25) had an in-field-recurrence and 8.0% (2/25) an ex-field/marginal recurrence (p=0.15).. After the administration of temozolomide concomitant with and adjuvant to radiotherapy in patients with glioblastoma, the pattern determined by [(18)F]FET-PET seems to be associated with MGMT methylation status.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Chemoradiotherapy; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Tumor Suppressor Proteins; Tyrosine

Early detection of treatment response in glioma patients after radiochemotherapy (RCX) is uncertain because treatment-related contrast enhancement in magnetic resonance imaging can mimic tumor progression. Positron emission tomography (PET) using the amino acid tracer [(18)F]fluoroethyltyrosine (FET) seems to be a promising tool for treatment monitoring. The aim of this prospective study was to evaluate the prognostic value of early changes of FET uptake after postoperative RCX in glioblastomas.. Twenty-two patients with glioblastoma were treated by surgery and subsequent RCX (whole dose 60-72 Gy). The FET-PET studies were performed before RCX, 7-10 days and 6-8 weeks after completion of RCX. Early treatment response in PET was defined as a decrease of the maximal tumor-to-brain ratio (TBR(max)) of FET uptake after RCX of more than 10%. The prognostic value of early changes of FET uptake after RCX was evaluated using Kaplan-Maier estimates for median disease-free survival and overall survival.. The median overall and disease-free survival of the patients was 14.8 and 7.8 months. There were 16 early responders in FET-PET (72.7%) and 6 nonresponders (27.3%). Early PET responders had a significantly longer median disease-free survival (10.3 vs. 5.8 months; p < 0.01) and overall survival ("not reached" vs. 9.3 months; p < 0.001). No statistically significant differences between the patient subgroups were found concerning the defined prognostic parameters.. FET-PET is a sensitive tool to predict treatment response in patients with glioblastomas at an early stage after RCX.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Combined Modality Therapy; Dacarbazine; Disease-Free Survival; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Prospective Studies; Radiopharmaceuticals; Temozolomide; Tyrosine