There is renewed interest in 18F-NaF bone imaging with PET or PET/CT. The current brief discussion focuses on the molecular mechanisms of 18F-NaF deposition in bone and presents model-based approaches to quantifying bone perfusion and metabolism in the context of preclinical and clinical applications of bone imaging with PET.
6-18 F-fluoro-L-dopa ( 18 F-FDOPA) measured with PET as a biomarker of amino acid uptake has been investigated in brain tumor imaging. The aims of the current study were to determine whether the degree of 18 F-FDOPA uptake in brain tumors predicted tumor grade and was associated with tumor proliferative activity in newly diagnosed and recurrent gliomas. Methods: Fifty-nine patients (40 men, 19 women; mean age 6 SD, 44.4 6 12.3 y) with newly diagnosed (n 5 22) or recurrent (n 5 37) gliomas underwent 18 F-FDOPA PET perioperatively. Tumor tissue was obtained by resection or biopsy in all patients. The tumor grade and Ki-67 proliferation index were obtained by standard pathology assays. Tumor 18 F-FDOPA uptake was quantified by determining various standardized uptake value (SUV) parameters (mean SUV, maximum SUV [SUVmax], mean values of voxels with top 20% SUVs, and tumor-to-normal-brain tissue ratios) that were then correlated with histopathologic grade and Ki-67 proliferation index. Results: Fifty-nine lesions in 59 patients were analyzed. 18 F-FDOPA uptake was significantly higher in high-grade than in low-grade tumors for newly diagnosed tumors (SUVmax, 4.22 6 1.30 vs. 2.34 6 1.35, P 5 0.005) but not for recurrent tumors that had gone through treatment previously (SUVmax, 3.36 6 1.26 vs. 2.67 6 1.18, P 5 0.22). An SUVmax threshold of 2.72 differentiated low-grade from high-grade tumors, with a sensitivity and specificity of 85% and 89%, respectively, using receiver-operating-characteristic curve analysis (area under the curve, 0.86). 18 F-FDOPA PET uptake correlated significantly with Ki-67 tumor proliferation index in newly diagnosed tumors (r 5 0.66, P 5 0.001) but not in recurrent tumors (r 5 0.14, P 5 0.41). Conclusion: 18 F-FDOPA uptake is significantly higher in high-grade than in low-grade tumors in newly diagnosed but not recurrent tumors that had been treated previously. A significant correlation between 18 F-FDOPA uptake and tumor proliferation in newly diagnosed tumors was observed, whereas this correlation was not identified for recurrent tumors. Thus, 18 F-FDOPA PET might serve as a noninvasive marker of tumor grading and might provide a useful surrogate of tumor proliferative activity in newly diagnosed gliomas.
L-3,4-Dihydroxy-6-18 F-fluoro-phenyl-alanine ( 18 F-FDOPA) is an amino acid analog used to evaluate presynaptic dopaminergic neuronal function. Evaluation of tumor recurrence in neurooncology is another application. Here, the kinetics of 18 F-FDOPA in brain tumors were investigated. Methods: A total of 37 patients underwent 45 studies; 10 had grade IV, 10 had grade III, and 13 had grade II brain tumors; 2 had metastases; and 2 had benign lesions. After 18 F-DOPA was administered at 1.5-5 MBq/kg, dynamic PET images were acquired for 75 min. Images were reconstructed with iterative algorithms, and corrections for attenuation and scatter were applied. Images representing venous structures, the striatum, and tumors were generated with factor analysis, and from these, input and output functions were derived with simple threshold techniques. Compartmental modeling was applied to estimate rate constants. Results: A 2-compartment model was able to describe 18 F-FDOPA kinetics in tumors and the cerebellum but not the striatum. A 3-compartment model with corrections for tissue blood volume, metabolites, and partial volume appeared to be superior for describing 18 F-FDOPA kinetics in tumors and the striatum. A significant correlation was found between influx rate constant K and late uptake (standardized uptake value from 65 to 75 min), whereas the correlation of K with early uptake was weak. High-grade tumors had significantly higher transport rate constant k 1 , equilibrium distribution volumes, and influx rate constant K than did low-grade tumors (P , 0.01). Tumor uptake showed a maximum at about 15 min, whereas the striatum typically showed a plateau-shaped curve. Patlak graphical analysis did not provide accurate parameter estimates. Logan graphical analysis yielded reliable estimates of the distribution volume and could separate newly diagnosed high-grade tumors from low-grade tumors. Conclusion: A 2-compartment model was able to describe 18 F-FDOPA kinetics in tumors in a first approximation. A 3-compartment model with corrections for metabolites and partial volume could adequately describe 18 F-FDOPA kinetics in tumors, the striatum, and the cerebellum. This model suggests that 18 F-FDOPA was transported but not trapped in tumors, unlike in the striatum. The shape of the uptake curve appeared to be related to tumor grade. After an early maximum, high-grade tumors had a steep descending branch, whereas low-grade tumors had a slowly declining curve, like that for the cerebellum but on a higher scale.
Background In patients with chronic coronary artery disease (CAD)
A three-compartment model with blood volume, metabolite, and partial volume corrections could adequately describe 18F-FLT kinetics in malignant brain tumors. Patients could be distinguished as having: (1) tumor-predominant or (2) treatment change-predominant lesions, with significantly different phosphorylation rates.
Background The incidence of myocardial inflammation in patients with unexplained cardiomyopathy referred for ventricular arrhythmias (VA) is unknown. Objective To report fasting PET scan findings in consecutive patients referred with unexplained cardiomyopathy and VA. Methods 18-FDG PET/CT scans with a >16 hour fasting protocol were prospectively ordered for patients referred for VA and unexplained cardiomyopathy (EF<55%). Patients with focal myocardial FDG uptake were labeled as arrhythmogenic inflammatory cardiomyopathy (AIC) and classified into four groups based on the presence of lymph node uptake (AIC+) and perfusion abnormalities (early vs late stage). Results Over a 3-year period, 103 PET scan were performed with 49% (AIC+=17, AIC=33) exhibiting focal FDG uptake. The mean age was 52±12 years with an EF of 36±16%. Patients with AIC were more likely to have a history of pacemaker (32% vs 6%, p=0.002) compared to those with normal PET. When biopsy was performed, histologic diagnosis revealed non-granulomatous inflammation in 6 patients and sarcoidosis in 18 patients. 90% of patients with AIC/AIC+ were prescribed immunosuppressive therapy and 58% underwent ablation. Correlation between areas of perfusion abnormalities and FDG uptake with electro-anatomic mapping was observed in 79% patients and MRI findings matched in only 33%. Conclusions Nearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggests that a significant proportion of patients labeled “idiopathic” may have occult arrhythmogenic inflammatory cardiomyopathy, which may benefit from early detection and immunosuppressive medical therapy.
This review addresses the specific contributions of nuclear medicine techniques, and especially positron emission tomography (PET), for diagnosis and management of brain tumors. 18F-Fluorodeoxyglucose PET has particular strengths in predicting prognosis and differentiating cerebral lymphoma from nonmalignant lesions. Amino acid tracers including 11C-methionine, 18F-fluoroethyltyrosine, and 18F-l-3,4-dihydroxyphenylalanine provide high sensitivity, which is most useful for detecting recurrent or residual gliomas, including most low-grade gliomas. They also play an increasing role for planning and monitoring of therapy. 18F-fluorothymidine can only be used in tumors with absent or broken blood–brain barrier and has potential for tumor grading and monitoring of therapy. Ligands for somatostatin receptors are of particular interest in pituitary adenomas and meningiomas. Tracers to image neovascularization, hypoxia, and phospholipid synthesis are under investigation for potential clinical use. All methods provide the maximum of information when used with image registration and fusion display with contrast-enhanced magnetic resonance imaging scans. Integration of PET and magnetic resonance imaging with stereotactic neuronavigation systems allows the targeting of stereotactic biopsies to obtain a more accurate histologic diagnosis and better planning of conformal and stereotactic radiotherapy.
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