Synthesis and Evaluation of 15-(4-(2-18FFluoroethoxy)phenyl)pentadecanoic Acid: a Potential PET Tracer for Studying Myocardial Fatty Acid Metabolism

摘要

15-(4-(2-[¹⁸F]fluoroethoxy)phenyl)pentadecanoic acid ([¹⁸F]>7) was synthesized as a PET probe for assessing myocardial fatty acid metabolism. The radiosynthesis of [¹⁸F]>7 was accomplished using a two step reaction, starting with the corresponding tosylate ester, methyl 15-(4-(2-(tosyloxy)ethoxy)phenyl)pentadecanoate (>5) and gave the radiolabeled fatty acid, [¹⁸F]>7 in a radiolabeling yield of 55 – 60% and a specific activity of > 2,000 Ci/mmol (decay corrected to EOB). The biological evaluation of [¹⁸F]>7 in rats displayed high uptake in heart (1.94%.ID/g at 5 min), which was higher than the uptake (%ID/g) in blood, lung, muscle, pancreas and brain. MicroPET studies of [¹⁸F]>7 in Sprague-Dawley rats demonstrated excellent images of the myocardium when compared with [¹¹C]palmitate images in the same animal. Moreover, the tracer kinetics of [¹⁸F]>7 paralleled those seen with [¹¹C]palmitate, with an early peak followed by biphasic washout. When compared to [¹¹C]palmitate, [¹⁸F]>7 exhibited a slower early clearance (0.17 ± 0.01 vs. 0.30 ± 0.02, P < 0.0001) and a significantly higher late clearance (0.0030 ± 0.0005 vs. 0.0006 ± 0.00013, P < 0.01). These initial studies suggest that [¹⁸F]>7 could be a potentially useful clinical PET tracer to assess abnormal myocardial fatty acid metabolism.