Usefulness of 11C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with 18F-FDG and 18F-FLT

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Many clinical PET studies have shown that increased 18F-FDG uptake is not specific to malignant tumors. 18F-FDG is also taken up in inflammatory lesions, particularly in granulomatous lesions such as sarcoidosis or active inflammatory processes after chemoradiotherapy, making it difficult to differentiate malignant tumors from benign lesions, and is the main source of falsepositive 18F-FDG PET findings in oncology. These problems may be overcome by multitracer studies using 39-deoxy- 39-18F-fluorothymidine (18F-FLT) or L-11C-methionine. However, 18F-FLT or 11C-methionine uptake in granulomatous lesions remains unclarified. In this study, the potentials of 18F-FLT and 11C-methionine in differentiating malignant tumors from granulomaswere comparedwith 18F-FDGusing experimental ratmodels. Methods: Dual-tracer tissue distribution studies using 18F-FDG and 3H-FLT (groups I and III) or 18F-FDG and 14C-methionine (groups II and IV)were performed on rats bearing both granulomas (Mycobacterium bovis bacillus Calmette-Gue´ rin [BCG]–induced) and hepatomas (KDH-8–induced) (groups I and II) or on rats bearing both turpentine oil–induced inflammation and hepatomas (groups III and IV). One hour after the injection of a mixture of 18F-FDG and 3H-FLT or of 18F-FDG and 14C-methionine, tissues were excised to determine the radioactivities of 18F-FDG, 3H-FLT, and 14C-methionine (differential uptake ratio). Results: Mature epithelioid cell granuloma formation and massive lymphocyte infiltration were observed in the granuloma tissue induced by BCG, histologically similar to sarcoidosis. The granulomas showed high 18F-FDG uptake comparable to that in the hepatomas (group I, 8.18 6 2.40 vs. 9.13 6 1.52, P 5 NS; group II, 8.43 6 1.45 vs. 8.91 6 2.32, P 5 NS). 14C-Methionine uptake in the granuloma was significantly lower than that in the hepatoma (1.31 6 0.22 vs. 2.47 6 0.60, P , 0.01), whereas 3H-FLT uptake in the granuloma was comparable to that in the hepatoma (1.98 6 0.70 vs. 2.30 6 0.67, P 5 NS). Mean uptake of 18F-FDG, 3H-FLT, and 14C-methionine was markedly lower in the turpentine oil–induced inflammation than in the tumor. Conclusion: 14C-Methionine uptake was significantly lower in the granuloma than in the tumor, whereas 18F-FDG and 3H-FLT were not able to differentiate granulomas from tumors. These results suggest that 14C-methionine has the potential to accurately differentiate malignant tumors frombenign lesions, particularly granulomatous lesions, providing a biologic basis for clinical PET studies.
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Usefulness of 11C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with 18F-FDG and 18F-FLT

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