1-11C-acetate as a PET radiopharmaceutical for imaging fatty acid synthase expression in prostate cancer.
Although it is accepted that the metabolic fate of 1-(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 (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-(11)C-acetate could be a marker for its expression.


METHODS
In vitro and in vivo uptake experiments in prostate tumor models with 1-(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-(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-(11)C-acetate uptake into the solid tumors and FAS expression levels was found.


CONCLUSIONS
Extensive involvement of the fatty acid synthesis pathway in 1-(11)C-acetate uptake in prostate tumors was confirmed, leading to a possible marker for FAS expression in vivo by noninvasive PET.
Vāvere
Amy L
AL
Division of Radiological Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Kridel
Steven J
SJ
Wheeler
Frances B
FB
Lewis
Jason S
JS
D000085:Acetates / Q000493:pharmacokinetics*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002244:Carbon / Q000493:pharmacokinetics*; D064429:Fatty Acid Synthases / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000085:Acetates; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D019275:Radiopharmaceuticals; C438206:carbon-11 acetate; D002244:Carbon; D064429:Fatty Acid Synthases