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1-^sup 11^C-Acetate as a PET Radiopharmaceutical for Imaging Fatty Acid Synthase Expression in Prostate Cancer
Ist Teil von
The Journal of nuclear medicine (1978), 2008-02, Vol.49 (2), p.327
Ort / Verlag
New York: Society of Nuclear Medicine
Erscheinungsjahr
2008
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Although it is accepted that the metabolic fate of 1-^sup 11^C-acetate is different in tumors than in myocardial tissue because of different clearance patterns, the exact pathway has not been fully elucidated. For decades, fatty acid synthesis has been quantified in vitro by the incubation of cells with ^sup 14^C-acetate. Fatty acid synthase (FAS) has been found to be overexpressed in prostate carcinomas, as well as other cancers, and it is possible that imaging with 1-^sup 11^C-acetate could be a marker for its expression. Methods: In vitro and in vivo uptake experiments in prostate tumor models with 1-^sup 11^C-acetate were performed both with and without blocking of fatty acid synthesis with either C75, an inhibitor of FAS, or 5-(tetradecyloxy)-2-furoic acid (TOFA), an inhibitor of acetyl-CoA carboxylase (ACC). FAS levels were measured by Western blot and immunohistochemical techniques for comparison. Results: In vitro studies in 3 different prostate tumor models (PC-3, LNCaP, and 22Rv1) demonstrated blocking of 1-^sup 11^C-acetate accumulation after treatment with both C75 and TOFA. This was further shown in vivo in PC-3 and LNCaP tumor-bearing mice after a single treatment with C75. A positive correlation between 1-^sup 11^C-acetate uptake into the solid tumors and FAS expression levels was found. Conclusion: Extensive involvement of the fatty acid synthesis pathway in 1-^sup 11^C-acetate uptake in prostate tumors was confirmed, leading to a possible marker for FAS expression in vivo by noninvasive PET. [PUBLICATION ABSTRACT]