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1-¹¹C-Acetate as a PET Radiopharmaceutical for Imaging Fatty Acid Synthase Expression in Prostate Cancer

Amy L. Vvere¹, Steven J. Kridel², Frances B. Wheeler² and Jason S. Lewis^1,3

¹ Division of Radiological Sciences, Washington University School of Medicine, St. Louis, Missouri; ² Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest University School of Medicine Winston-Salem, North Carolina; and ³ Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri

Correspondence: For correspondence or reprints contact: Jason S. Lewis, PhD, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8225, 510 S. Kingshighway Blvd., St. Louis, MO 63110. E-mail: j.s.lewis{at}wustl.edu

Although it is accepted that the metabolic fate of 1-¹¹C-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 ¹⁴C-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 1-¹¹C-acetate could be a marker for its expression. Methods: In vitro and in vivo uptake experiments in prostate tumor models with 1-¹¹C-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 1-¹¹C-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 1-¹¹C-acetate uptake into the solid tumors and FAS expression levels was found. Conclusion: Extensive involvement of the fatty acid synthesis pathway in 1-¹¹C-acetate uptake in prostate tumors was confirmed, leading to a possible marker for FAS expression in vivo by noninvasive PET.

Key Words: 1-¹¹C-acetate • fatty acid synthase • C75 • TOFA

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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