17-[4-(2-[18F]Fluoroethyl)-1H-1,2,3-triazol-1-yl]-6-thia-heptadecanoic Acid: A Potential Radiotracer for the Evaluation of Myocardial Fatty Acid Metabolism

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• 作者：Dong Hyun Kim ; Yearn Seong Choe ; Joon Young Choi ; Yong Choi ; Kyung-Han Lee ; Byung-Tae Kim
• 刊名：Bioconjugate Chemistry
• 出版年：2009
• 出版时间：June 17, 2009
• 年：2009
• 卷：20
• 期：6
• 页码：1139-1145
• 全文大小：134K
• 年卷期：v.20,no.6(June 17, 2009)
• ISSN：1520-4812

文摘

In this study, we synthesized 17-[4-(2-[¹⁸F]fluoroethyl)−1H-1,2,3-triazol-1-yl]-6-thia-heptadecanoic acid ([¹⁸F]1), a PET radiotracer for the evaluation of fatty acid metabolism. [¹⁸F]1 was synthesized in 20−26% decay-corrected radiochemical yields from 17-azido 6-thia-heptadecanoic acid (9) and 4-[¹⁸F]fluoro-1-butyne using click chemistry. The tissue distribution of [¹⁸F]1 in mice showed high radioactivity accumulation in heart (3.70%ID/g at 1 min, 3.28%ID/g at 10 min, and 3.01%ID/g at 60 min postinjection), a prolonged myocardial elimination half-life (>60 min), and a maximal heart-to-blood uptake ratio at 5 min postinjection (5.55). Pretreatment with etomoxir, a carnitine palmitoyl transferase (CPT) I inhibitor, reduced myocardial radioactivity uptake at 30 min postinjection by 53%, suggesting that [¹⁸F]1 was transported into the mitochondria. Analyses of heart tissue samples showed that most of the radioactivity was present in a tissue pellet (62−63%) after homogenization in CHCl₃−CH₃OH followed by extraction with 40% urea and 5% H₂SO₄, which was mostly precipitated with addition of 50% trichloroacetic acid (TCA). These results suggest that [¹⁸F]1 undergoes metabolic trapping via β-oxidation in myocardium and, thus, suggest that it has potential use as a PET radiotracer for the evaluation of myocardial fatty acid metabolism.