Usefulness of 11C-methionine for differentiating tumors from granulomas in experimental rat models: a comparison with 18F-FDG and 18F-FLT.
Many clinical PET studies have shown that increased (18)F-FDG uptake is not specific to malignant tumors. (18)F-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 false-positive (18)F-FDG PET findings in oncology. These problems may be overcome by multitracer studies using 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) or l-(11)C-methionine. However, (18)F-FLT or (11)C-methionine uptake in granulomatous lesions remains unclarified. In this study, the potentials of (18)F-FLT and (11)C-methionine in differentiating malignant tumors from granulomas were compared with (18)F-FDG using experimental rat models.


METHODS
Dual-tracer tissue distribution studies using (18)F-FDG and (3)H-FLT (groups I and III) or (18)F-FDG and (14)C-methionine (groups II and IV) were performed on rats bearing both granulomas (Mycobacterium bovis bacillus Calmette-Guérin [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 (18)F-FDG and (3)H-FLT or of (18)F-FDG and (14)C-methionine, tissues were excised to determine the radioactivities of (18)F-FDG, (3)H-FLT, and (14)C-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 (18)F-FDG uptake comparable to that in the hepatomas (group I, 8.18 +/- 2.40 vs. 9.13 +/- 1.52, P = NS; group II, 8.43 +/- 1.45 vs. 8.91 +/- 2.32, P = NS). (14)C-Methionine uptake in the granuloma was significantly lower than that in the hepatoma (1.31 +/- 0.22 vs. 2.47 +/- 0.60, P < 0.01), whereas (3)H-FLT uptake in the granuloma was comparable to that in the hepatoma (1.98 +/- 0.70 vs. 2.30 +/- 0.67, P = NS). Mean uptake of (18)F-FDG, (3)H-FLT, and (14)C-methionine was markedly lower in the turpentine oil-induced inflammation than in the tumor.


CONCLUSIONS
(14)C-Methionine uptake was significantly lower in the granuloma than in the tumor, whereas (18)F-FDG and (3)H-FLT were not able to differentiate granulomas from tumors. These results suggest that (14)C-methionine has the potential to accurately differentiate malignant tumors from benign lesions, particularly granulomatous lesions, providing a biologic basis for clinical PET studies.
Zhao
Songji
S
Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Kuge
Yuji
Y
Kohanawa
Masashi
M
Takahashi
Toshiyuki
T
Zhao
Yan
Y
Yi
Min
M
Kanegae
Kakuko
K
Seki
Koh-Ichi
K
Tamaki
Nagara
N
D000818:Animals; D002250:Carbon Radioisotopes; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000209:etiology; D045744:Cell Line, Tumor; D003937:Diagnosis, Differential; D015224:Dideoxynucleosides; D019788:Fluorodeoxyglucose F18; D006099:Granuloma / Q000000981:diagnostic imaging* / Q000382:microbiology; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000209:etiology; D008297:Male; D008715:Methionine; D009163:Mycobacterium bovis; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D014425:Turpentine
D002250:Carbon Radioisotopes; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D008715:Methionine; C002854:alovudine; D014425:Turpentine