Human studies of dopamine D2/D3 receptors using 18F-fallypride-PET in normal volunteers were performed to evaluate brain distribution in striatal and extrastriatal regions, evaluate metabolites in blood plasma, establish PET imaging protocol for this new radiotracer, evaluate graphical methods of analysis to quantitate D2/D3 receptors, and assess the ability of 18F-fallypride to measure changes in D2/D3 receptors with aging as a model. Subjects (6; 21-63 years) had a PET scan on a Siemens HR+ scanner with 18F-fallypride and a T1-weighted MRI scan on a 1.5T GE scanner for purposes of anatomical coregistration with PET. A 3-h PET scan with 18F-fallypride (0.07 mCi/Kg) was carried out on each subject and repeated in 4-6 weeks. Arterial or arterialized venous blood was obtained in all subjects in order to evaluate blood activity levels and analyze metabolites in the plasma. Brain regions-of-interest were identified and drawn using PET and PET-MR coregistered images. PET data was analyzed using graphical methods in which cerebellum was used as the reference region providing distribution volume ratios (DVR) from which binding potential (BP) was derived and used as a measure of concentration of receptors. Distribution of 18F-fallypride was consistent in all subjects studied and the rank order of receptor concentration was putamen > caudate > thalamus = pituitary > amygdala > colliculi > substantia nigra > hippocampus = temporal cortex > parietal cortex = occipital cortex = orbitofrontal cortex. For younger subjects, BP ranged from 37 for the putamen to 0.4 for orbitofrontal cortex, with a test-retest error of about 10%. Both hydrophilic and lipophilic metabolites were observed in arterial blood plasma and analyses showed approx. 30-40% of plasma radioactivity at 3 h was 18F-fallypride. With aging, all brain regions exhibited a significant decrease (>10% per decade) in binding of 18F-fallypride. PET studies with 18F-fallypride are thus suitable to study changes in D2/D3 receptors in striatal and extrastriatal brain regions.
Positron emission tomography (PET) using L-[methyl-(11)C]-methionine (MET) is the most popular amino acid imaging modality in oncology, although its use is restricted to PET centers with an in-house cyclotron facility. This review focuses on the role of MET-PET in imaging of cerebral gliomas. The biological background of tumor imaging with methionine is discussed with particular emphasis on cellular amino acid transport, amino acid utilization in brain, normal metabolism of methionine, and its alterations in cancer. The role of MET-PET in clinical management of cerebral gliomas in initial diagnosis, differentiation of tumor recurrence from radiation injury, grading, prognostication, tumor-extent delineation, biopsy planning, surgical resection and radiotherapy planning, and assessment of response to therapy is also reviewed in detail.
The aim of this study was to compare the grading and prognostic value of L-[methyl-11 C]-methionine ( 11 C-MET) PET in glioma patients with 18 F-FDG PET and contrast-enhanced MRI. Methods: Patients (n 5 102) with histopathologically confirmed gliomas were followed up for an average of 34.6 6 3.8 mo after PET. The median survival was 18 6 4.7 mo in the high-grade glioma group and 58 6 27 mo in the low-grade glioma group. Patients underwent 18 F-FDG PET, 11 C-MET PET, and MRI in the diagnostic and preoperative stage. The ratio of the mean standardized uptake value in the tumor to mean standardized uptake value in contralateral normal cortex (T/N ratio) was calculated. Kaplan-Meier survival analysis and ANOVA were performed. Results: T/N ratios for 11 C-MET PET and 18 F-FDG PET were significantly higher in high-grade gliomas than in low-grade gliomas (2.15 6 0.77 vs. 1.56 6 0.74, P , 0.001, and 0.85 6 0.61 vs. 0.63 6 0.37, P , 0.01, respectively). Median survival was 19 6 5.4 mo in patients with a T/N ratio greater than 1.51 for 11 C-MET PET and 58 6 26.7 mo in those with a T/N ratio less than 1.51 (P 5 0.03). Among the LGGs, median survival was lower in patients with a mean T/N ratio greater than 1.51 for 11 C-MET PET (16 6 10 mo; 95% confidence interval, 1-36 mo) than in those with a T/N ratio less than 1.51 (P 5 0.04). No significant difference in survival in LGGs was based on 18 F-FDG uptake and MRI contrast enhancement. Conclusion: 11 C-MET PET can predict prognosis in gliomas and is better than 18 F-FDG PET and MRI in predicting survival in LGGs.
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