Synthesis and evaluation of 15-(4-(2-[¹8F]Fluoroethoxy)phenyl)pentadecanoic acid: a potential PET tracer for studying myocardial fatty acid metabolism.

ABSTRACT

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 >2000 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.