fluorocholine and Glioma

To study the association of metabolic features of F-fluorocholine in gliomas with histopathological and molecular parameters, progression-free survival (PFS) and overall survival (OS).. Prospective multicenter and nonrandomized study (Functional and Metabolic Glioma Analysis). Patients underwent a basal F-fluorocholine PET/CT and were included after histological confirmation of glioma. Histological and molecular profile was assessed: grade, Ki-67, isocitrate dehydrogenase status and 1p/19q codeletion. Patients underwent standard treatment after surgery or biopsy, depending on their clinical situation. Overall survival and PFS were obtained after follow-up. After tumor segmentation of PET images, SUV and volume-based variables, sphericity, surface, coefficient of variation, and multilesionality were obtained. Relations of metabolic variables with histological, molecular profile and prognosis were evaluated using Pearson χ and t test. Receiver operator caracteristic curves were used to obtain the cutoff of PET variables. Survival analysis was performed using Kaplan-Meier and Cox regression analysis.. Forty-five patients were assessed; 38 were diagnosed as having high-grade gliomas. Significant differences of SUV-based variables with isocitrate dehydrogenase status, tumor grade, and Ki-67 were found. Tumor grade, Ki-67, SUVmax, and SUVmean were related to progression. Kaplan-Meier analysis revealed significant associations of SUVmax, SUVmean, and multilesionaly with OS and PFS. SUVmean, sphericity, and multilesionality were independent predictors of OS and PFS in Cox regression analysis.. Metabolic information obtained from F-fluorocholine PET of patients with glioma may be useful in the prediction of tumor biology and patient prognosis.

Topics: Choline; Chromosome Deletion; Disease Progression; Female; Glioma; Humans; Isocitrate Dehydrogenase; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Grading; Positron Emission Tomography Computed Tomography; Progression-Free Survival; Prospective Studies

The aim of this study was to assess the prognostic performance of postoperative 18F-fluorocholine PET/CT in patients with high-grade glioma (HGG).. Patients with HGG who underwent preoperative and postoperative 18F-fluorocholine PET/CT were prospectively enrolled in the study. Postoperative MRI was classified as complete versus incomplete resection. Postoperative 18F-fluorocholine PET/CT was classified as negative (complete) or positive for metabolic residual tumor (incomplete resection) using a 5-point score system. The correlation of positive locations on PET/CT with the sites of subsequent tumor recurrence was evaluated. The concordance of postoperative imaging techniques (Cohen κ) and their relation with progression-free survival and overall survival were assessed using Kaplan-Meier method and Cox regression analysis.. Fifty-one studies, belonging to 47 patients, were assessed. Four patients underwent 2 postoperative 18F-fluorocholine PET/CT scans as they needed a second tumor resection for recurrence. In the follow-up, 42 patients progressed, and 37 died. Concordance between postoperative PET/CT and MRI assessment was poor. Resection grade on MRI did not show any significant association with prognosis. In multivariate analysis, only age and postoperative PET/CT showed significant association with progression-free survival (hazard ratio [HR], 1.03 [1.01-1.06, P = 0.006] and 1.88 [0.96-3.71, P = 0.067], respectively) and overall survival (HR, 1.04 [1.01-1.07, P = 0.004] and 2.63 [1.22-5.68, P = 0.014], respectively). Postoperative positive 18F-fluorocholine PET/CT locations correlated with the sites of subsequent tumor recurrence in 81.82% of cases.. Postoperative 18F-fluorocholine PET/CT seems superior to postoperative MRI in the outcome prediction of patients with HGG, outperforming it in the identification of the most probable location of tumor recurrence.

Topics: Choline; Glioma; Humans; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Prognosis

Gliomas are characterized by an inherent diffuse and irregular morphology that prevents defining a boundary between tumor and healthy tissue, both in imaging assessment and surgical field. The effective identification of the extent of the disease in diffuse and multiple gliomas is crucial for their management but doing so by radiological means can be challenging. We present a broad spectrum of diffuse and multiple gliomas using 18F-fluorocholine PET/CT, demonstrating the potential of metabolic imaging in the evaluation of these gliomas, with implications in patient clinical management and outcome.

Topics: Choline; Glioma; Humans; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals

The aim of this study was to analyze the usefulness of 18 F-fluorocholine PET/CT in the early diagnosis of tumor recurrence, increasing the diagnosis confidence of MRI.. Patients with a previous gross total resection of glioma and the first suspicious or doubtful for recurrence MRI were prospectively included and subjected to 18 F-fluorocholine PET/CT. An independent and combined assessment of 18 F-fluorocholine PET/CT and multimodal MRI was performed classifying the studies as positive or negative for tumor recurrence. Final diagnosis (recurrence or not) was obtained by histological confirmation or clinical and imaging follow-up. The relation of SUV max and tumor-to-background ratio with progression, the diagnostic performance of imaging techniques, and their concordance (κ Cohen) were analyzed.. Twenty-four studies on 21 patients were assessed. Recurrence was diagnosed in 20 cases. PET/CT was positive in 23 cases (3 false positive), whereas MRI was positive in 15 cases (1 false positive). MRI was false negative in 6 cases. There was no false negative on 18 F-fluorocholine PET/CT. Accuracy of PET/CT versus MRI was 87.5% and 70.8%, respectively. The combined evaluation of both techniques did not show any advantage with respect to PET/CT results alone. The concordance between both imaging techniques was low (κ = 0.135; P = 0.375). SUV max and tumor-to-background ratio were related to recurrence (areas under the curve of 0.844 [ P = 0.033] and 0.869 [ P = 0.022], respectively).. 18 F-fluorocholine PET/CT was helpful for increasing the diagnostic confidence in the cases of MRI doubtful for recurrence in order to avoid a delayed diagnosis.

Topics: Choline; Early Diagnosis; Glioma; Humans; Neoplasm Recurrence, Local; Pilot Projects; Positron Emission Tomography Computed Tomography

To investigate the diagnostic accuracy of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) and fluoromethyl-(18F)-dimethyl-2-hydroxyethyl-ammonium chloride (18F-FCH) computed tomography (CT) in patients with primary low-grade gliomas (LGG).. The study enrolled patients with magnetic resonance imaging (MRI)-suspected LGG. Patients underwent both 18F-FET and 18F-FCH positron emission tomography (PET)-CT. Brain PET-CT was performed according to standard protocol - 20 minutes after intravenous injection of 185 MBq of 18F-FET and 185 MBq of 18F-FCH PET. Surgery and pathohistological diagnosis were performed in the next two weeks.. We observed significantly better concordance between tumor histology and 18F-FET PET (weighted Kappa 0.74) compared with both 18F-FCH (weighted Kappa 0.15) and MRI (weighted Kappa 0.00). Tumor histology was significantly associated with 18F-FET (odds ratio 12.87; 95% confidence interval [CI], 0.49-333.70; P=0.013, logistic regression analysis). Receiver operating characteristic curve analysis comparing 18F-FCH (area under the curve [AUC] 0.625, 95% CI 0.298-0.884) and 18F-FET (AUC 0.833, 95% CI 0.499-0.982) showed better diagnostic properties of 18F-FET (AUC difference 0.208, 95% CI -0.145 to 0.562, P=0.248).. Performing PET-CT in patients with newly diagnosed LGG should be preceded by a selection of an appropriate radiopharmaceutical. 18F-FET seems to be more accurate than 18F-FCH in the LGG diagnosis.

Topics: Brain Neoplasms; Choline; Glioma; Humans; Magnetic Resonance Imaging; Pilot Projects; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

Gliomas are characterized by intratumoral histological heterogeneity, coexisting foci of low and high grade. First, in low-grade gliomas, neoangiogenesis has not yet developed and cellularity is low, so alterations on perfusion MRI may not be present. Second, a non-negligible number of high-grade gliomas show none, patchy, or weak contrast enhancement on MRI, so they can be misdiagnosed as low-grade glioma, preventing their correct management. We present 4 cases of patients in which F-fluorocholine PET defined the anaplastic tumor component and therefore the tumor aggressiveness, solving the limitations of MRI.

Topics: Brain Neoplasms; Choline; Glioma; Humans; Magnetic Resonance Imaging; Neoplasm Grading; Neovascularization, Pathologic; Positron-Emission Tomography

Postoperative assessment is crucial in the imaging follow-up and prognosis in patients with glioma. Whereas grade of resection is defined attending to the gadolinium enhancement in early postoperative MRI, no metabolical criteria exist for postoperative PET interpretation. Based on our prospective and multicenter FuMeGA (Functional and Metabolic Glioma Analysis) ongoing study, we propose criteria for the visual interpretation of F-fluorocholine PET scans in patients undergoing brain tumor resection. The different imaging characteristics between MRI and PET may explain the discordances regarding to the postresection status with both techniques.

Topics: Adult; Aged; Brain Neoplasms; Choline; Female; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Postoperative Period

Ischemic complications after resection of high-grade glioma are frequent and may constitute potential cause of false-positive results in postsurgical evaluation using F-fluorocholine PET/CT. On the other hand, hypoxia caused by ischemia promotes invasive glioma growth. We present 3 cases of patients with different grades of ischemic injury after resection of high-grade glioma. The combined interpretation of diffusion-weighted imaging and apparent diffusion coefficient map on MRI, in this clinical setting, is mandatory to avoid PET/CT misinterpretations.

Topics: Adult; Brain Ischemia; Brain Neoplasms; Choline; Diagnosis, Differential; Female; Glioma; Humans; Male; Neoplasm Grading; Neoplasm, Residual; Positron Emission Tomography Computed Tomography

High-grade glioma is a very aggressive and infiltrative tumor in which complete resection is a chance for a better outcome. We present the case of a 57-year-old man with a brain lesion suggestive of high-grade glioma. Brain MRI and F-fluorocholine PET/CT were performed previously to plan the surgery. Surgery was microscope assisted after the administration of 5-aminolevulinic acid. Postsurgery brain MRI and PET were blind evaluated to the surgery results and reported as probably gross total resection.

Topics: Aminolevulinic Acid; Brain; Brain Neoplasms; Choline; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Positron Emission Tomography Computed Tomography

The follow-up of treated low-grade glioma (LGG) requires the evaluation of subtle clinical changes and MRI results. When the result is inconclusive, additional procedures are required to assist decision-making, such as the use of advanced MRI (aMRI) sequences and nuclear medicine scans (SPECT and PET). The aim of this study was to determine whether incorporating (18)F-fluorocholine PET/CT in the follow-up protocol for treated LGG improves diagnostic accuracy and clinical utility.. This was a prospective case-series study in patients with treated LGG during standard follow-up with indeterminate clinical and/or radiological findings of tumour activity. All patients underwent clinical evaluation, aMRI, (201)Tl-SPECT and (18)F-fluorocholine PET/CT. Images were interpreted by visual evaluation complemented with semiquantitative analysis.. Between January 2012 and December 2013, 18 patients were included in this study. The final diagnosis was established by histology (five surgical specimens, one biopsy specimen) or by consensus of the Neuro-Oncology Group (11 patients) after a follow-up of >6 months (mean 14.9 ± 2.72 months). The global diagnostic accuracies were 90.9% for aMRI (38.8% inconclusive), 69.2 % for (201)Tl-SPECT (11.1% inconclusive), and 100% for (18)F-fluorocholine PET/CT. (201)Tl-SPECT led correctly to a change in the initial approach in 38.9% of patients but might have led to error in 27.8%. The use of (18)F-fluorocholine PET/CT alone rather than (201)Tl-SPECT led correctly to a change in the approach suggested by routine follow-up in 72.2% of patients and endorsed the approach in the remaining 27.8%.. Our results support the need to complement structural MRI with aMRI and nuclear medicine procedures in selected patients. (18)F-Fluorocholine PET/CT can be useful in the individualized management of patients with treated LGG with uncertain clinical and/or radiological evidence of tumour activity.

Topics: Adult; Brain Neoplasms; Choline; Female; Glioma; Humans; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Thallium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Primary brain tumors (PBT), in particular gliomas, are among the most difficult neoplasms to treat, necessitating good quality imaging to guide clinicians at many junctures. Current imaging modalities, including [18F] fluorodeoxyglucose (FDG) PET/CT, MRI and MR spectroscopy (MRS), have various limitations, particularly with regard to differentiating tumor from radiation induced necrosis (RIN) and from normal cerebral metabolic uptake. [18F] fluorocholine (FCH) is an analog of choline with potentially optimal imaging characteristics, as pharmacokinetic studies with FCH conducted in patients showed minimal FCH uptake by normal brain parenchyma, whereas high-grade tumors are known to have increased choline uptake. We present two cases of our early experience with FCH PET/CT for patients with PBT and discuss the potential use and comparative limitations of this imaging modality.

Topics: Brain Neoplasms; Choline; Fatal Outcome; Female; Fluorine Radioisotopes; Glioblastoma; Glioma; Humans; Magnetic Resonance Imaging; Middle Aged; Neoplasm Recurrence, Local; Oligodendroglioma; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed

A 22-year-old man diagnosed with neurofibromatosis-I was admitted to the neurology department because of progressive hemianopsia and chronic headache. Magnetic resonance imaging, magnetic resonance spectroscopy (MRS), and F-18 fluorocholine revealed a splenial mass with imaging features compatible with malignant astrocytoma. At follow-up examination, the sharp decrease in F-18 fluorocholine uptake and in choline/creatine ratio supported a conservative management. Molecular imaging of optic pathway gliomas may be a valuable tool in the selection of therapeutic options.

Topics: Brain; Choline; Glioma; Humans; Male; Neurofibromatosis 1; Optic Nerve; Positron-Emission Tomography; Tomography, X-Ray Computed; Young Adult

[(18)F]Fluorocholine ([(18)F]FCH) was developed as an analog of [(11)C]choline for tumor imaging; however, its metabolic handling remains ill defined. In this study, the metabolism of [(18)F]FCH is evaluated in cultured 9L glioma cells and Fisher 344 rats bearing 9L glioma tumors.. 9L glioma cells were incubated with [(18)F]FCH and [(14)C]choline under normoxic and hypoxic (1% O(2)) conditions and analyzed for metabolic fate. [(18)F]FCH and [(14)C]choline kinetics and metabolism were studied in Fisher 344 rats bearing subcutaneous 9L tumors.. [(18)F]FCH and [(14)C]choline were similarly metabolized in 9L cells in both normoxic and hypoxic conditions over a 2-h incubation period. In normoxia, radioactivity was predominantly in phosphorylated form for both tracers after 5-min incubation. In hypoxia, the tracers remained mainly in nonmetabolized form at early timepoints (<20 min). Slow dephosphorylation of intracellular [(18)F]phosphofluorocholine (0.043-0.060 min(-1)) and [(14)C]phosphocholine (0.072-0.088 min(-1)) was evidenced via efflux measurements. In rat, both [(18)F]FCH and [(14)C]choline showed high renal and hepatic uptake. Blood clearance of both tracers was rapid with oxidative metabolites, [(18)F]fluorobetaine and [(14)C]betaine, representing the majority of radiolabel in plasma after 5 min postinjection. Oxidation (in liver) and lipid incorporation (in lung) were somewhat slower for [(18)F]FCH relative to [(14)C]choline. The majority of radiolabel in hypoxic subcutaneous tumor, as in hypoxic cultured 9L cells, was found as nonmetabolized [(18)F]FCH and [(14)C]choline.. [(18)F]FCH mimics choline uptake and metabolism by 9L glioma cells and tumors. However, subtle changes in biodistribution, oxidative metabolism, dephosphorylation, lipid incorporation, and renal excretion show moderate effects of the presence of the radiofluorine atom in [(18)F]FCH. The decrease in phosphorylation of exogenous choline by cancer cells should be considered in interpretation of positron emission tomography images in characteristically hypoxic tumors.

Topics: Animals; Cell Line, Tumor; Choline; Glioma; Male; Metabolic Clearance Rate; Organ Specificity; Radionuclide Imaging; Rats; Rats, Inbred F344; Tissue Distribution

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

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