Exploration of the dominant fatty acid metabolic pathway for PET imaging of prostate cancer

1122 Objectives Fatty acid oxidation has been suggested as the dominant bioenergetic pathway in prostate cancer wherein glucose consumption is dormant until the disease becomes disseminative. The aim of this study is to explore the possibility of targeting the dominant bioenergetic pathway for prostate cancer imaging, which was tested by experiments performed with a reported PET tracer for myocardial fatty acid utilization studies, 14(R,S)-18F-fluoro-6-thia-heptadecanoic acid (18F-FTHA). Methods The radiotracer, 18F-FTHA, was prepared from the precursor of 16α-[[(trifluoromethyl)sulfonyl]oxy]-3,3-(ethylenedioxy)androstan-17-one in radiochemical yields of > 35% and its radiochemical purity was > 99% after purification. Three PC3 tumor bearing mice were intravenously administered 3.7 MBq of 18F-FTHA formulated in 4% of albumin saline solution. A dynamic PET/CT scan (0 ‒ 40 min) was immediately conducted on each mouse after injection, followed by a 15-min static PET/CT scan at 2 h post-injection (p.i.). The images were reconstructed and quantitatively analyzed with the manufacturer’s software. Results Immediately after administration of 18F-FTHA, the radioactivity was observed to accumulate in the peripherals of tumor in addition to the expected uptake in the heart, liver, and bone due to the nature of 18F-FTHA. Gradually, more activity was showing up in the tumor interior. This phenomenon can be attributed to the tumor blood vessel environment and the slow distribution of 18F-FTHA inside the tumors as resulted from the formation of 18F-FTHA-albumin complex. The tumor uptake peaked at 1.2 ± 0.33 at 40 min p.i. The tumor-to-muscle ratios increased from 1.5 to 2.3 within 0 ‒ 40 min p.i., and then slightly dropped to 1.7 at 2 h p.i. Conclusions Our preliminary data showed the potential of using fatty acid based PET tracers for prostate cancer imaging. However, because of the physiology and physical location of the prostate, the pharmacokinetic parameters and tumor targeting ability of the tracers need to be optimized for the purpose. Research Support This study was partially supported by the Dr. Jack Krohmer Professorship Funds.