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

15-(4-(2-[1?F]fluoroethoxy)phenyl)pentadecanoic acid ([1?F]7) was synthesized as a PET probe for assessing myocardial fatty acid metabolism. The radiosynthesis of [1?F]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, [1?F]7 in a radiolabeling yield of 55-60% and a specific activity of >2000 Ci/mmol (decay corrected to EOB). The biological evaluation of [1?F]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 [1?F]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 [1?F]7 paralleled those seen with [11C]palmitate, with an early peak followed by biphasic washout. When compared to [11C]palmitate, [1?F]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 [1?F]7 could be a potentially useful clinical PET tracer to assess abnormal myocardial fatty acid metabolism.     

Synthesis and evaluation of 6-(3-[18F]fluoro-2-hydroxypropyl)-substituted 2-pyridylbenzothiophenes and 2-pyridylbenzothiazoles as potential PET tracers for imaging Aβ plaques

3-[¹⁸F]Fluoro-2-hydroxypropyl substituted compounds were synthesized and evaluated as novel ¹⁸F-labeled PET tracers for imaging Aβ plaque in a living brain. All compounds exhibited high binding affinities toward the synthetic Aβ_1–42 aggregate and/or Alzheimer’s disease brain homogenate. In the microPET study with normal mice, the 3-[¹⁸F]fluoro-2-hydroxypropyl substituted compounds resulted in fast brain washout by reducing the lipophilicities of the compounds. Intriguingly, (S)-configured PET tracers, (S)-[¹⁸F]1b and (S)-[¹⁸F]1c, exhibited a 2.8 and 4.0-fold faster brain washout rate at a peak/30 min in the mouse brain than the corresponding (R)-configured PET tracers despite there being no meaningful difference in binding affinities toward Aβ plaque. A further evaluation of (S)-[¹⁸F]1c with healthy rhesus monkeys also revealed excellent clearance from the frontal cortex with ratios of 7.0, 16.0, 30.0 and 49.0 at a peak/30, 60, 90, and 120 min, respectively. These results suggest that (S)-[¹⁸F]1c may be a potential PET tracer for imaging Aβ plaque in a living brain.