2-¹⁸F-Fluoropropionic Acid as a PET Imaging Agent for Prostate Cancer

¹ Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York

^* To whom correspondence should be addressed. E-mail: pillarsn{at}mskcc.org.

	Abstract

There is a high interest in developing an ¹⁸F-labeled PET tracer that can aid in diagnosis and therapy monitoring of prostate cancer. In the current study, we have evaluated the potential of 2-¹⁸F-fluoropropionic acid (¹⁸F-FPA) as a PET tracer for imaging prostate cancer. Methods: ¹⁸F-FPA was synthesized starting from methyl-2-bromopropionate. Small-animal PET studies were performed on mice with CWR22rv1, PC-3, DU-145, and LNCaP prostate xenografts, and comparison of imaging characteristics of ¹⁸F-FPA with ¹⁸F-FDG uptake is reported. Biodistribution studies with ¹⁸F-FPA were performed on mice with CWR22rv1 xenografts and compared with ¹⁴C-acetate. Results: ¹⁸F-FPA was synthesized in 44% overall radiochemical yield (decay-corrected). Small-animal PET studies revealed that ¹⁸F-FPA can delineate both androgen-dependent and androgen-independent prostate xenografts with high tumor-to-background ratios. Comparative imaging studies demonstrate the superior performance of ¹⁸F-FPA over ¹⁸F-FDG for imaging prostate cancer, with excellent tumor-to-background contrast. Biodistribution studies show that tumor uptake of the tracer was 5.52 ± 0.35, 5.53 ± 0.42, 5.74 ± 0.54, and 5.34 ± 0.19 percentage injected dose (%ID) per gram at 1, 2, 3, and 4 h, respectively, after injection. The %ID/g values for ¹⁸F-FPA and ¹⁴C-acetate 1 h after tail vein injection were 7.08 ± 0.80 and 0.36 ± 0.08 in tumor, and the corresponding tumor-to-muscle ratios were 1.94 and 2.06, respectively. Conclusion: The data presented here indicate that ¹⁸F-FPA accumulates in prostate cancers with high tumor-to-background ratios. ¹⁸F-FPA has potential for use in the clinical diagnosis of prostate cancer in humans.

Key Words: prostate cancer, PET, ¹¹C-acetate, 2-¹⁸F-fluoropropionic acid, CWR22rv1