Synthesis and Evaluation of 15-(4-(2-[18F]Fluoroethoxy)phenyl)pentadecanoic Acid: A Potential PET Tracer for Studying Myocardial Fatty Acid Metabolism

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• 作者：Zhude Tu ; Shihong Li ; Terry L. Sharp ; Pilar Herrero ; Carmen S. Dence ; Robert J. Gropler ; Robert H. Mach
• 刊名：Bioconjugate Chemistry
• 出版年：2010
• 出版时间：December 15, 2010
• 年：2010
• 卷：21
• 期：12
• 页码：2313-2319
• 全文大小：220K
• 年卷期：v.21,no.12(December 15, 2010)
• ISSN：1520-4812

文摘

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.