Synthesis of [18F]-Labeled (6-Fluorohexyl)triphenylphosphonium Cation as a Potential Agent for Myocardial imaging using Positron Emission Tomography
Synthesis of [18F]-Labeled (6-Fluorohexyl)triphenylphosphonium Cation as a Potential Agent for Myocardial imaging using Positron Emission Tomography
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DOI：
10.1021/bc2004439
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发表时间：
2012-03-01
影响因子：
4.7
通讯作者：
Min, Jung-Joon
中科院分区：
文献类型：
--
作者：
Kim, Dong-Yeon;Kim, Hee-Jung;Min, Jung-Joon
亲脂性阳离子如鳞盐穿透质膜和线粒体膜的疏水屏障，并响应于负的跨膜内电位而在线粒体中积累。因此，作为新开发的非侵入性显像剂，[F-18]标记的鏻盐可作为分子“电压传感器”探针，以研究线粒体的作用，特别是在心肌疾病中。本研究报告了放射合成的（6-氟己基）三苯基鏻盐（3）作为一种潜在的药物，心肌显像，通过使用正电子发射断层扫描（PET）。通过三步亲核取代反应合成了参考化合物（6-[F-18]氟己基）三苯基鏻盐（[F-18]3），产率为74%。在Kryptofix 2.2.2和K2 CO 3存在下，通过无载体添加的[F-18]氟化物与前体己烷-1，6-二基双（4-甲基苯磺酸盐）的两步亲核取代反应对参比化合物进行放射性标记。以15-20%的产率合成放射性标记的化合物。经HPLC分析，放射化学纯度>98%，比活度>6.10-6.47 TBq/μ mol。细胞摄取试验显示心肌细胞优先摄取[F-18]3。[F-18]3在小鼠和大鼠体内的生物分布和micro-PET成像研究结果显示，[F-18]3优先在心肌中蓄积。结果表明，这种化合物将是一个有前途的候选心肌显像。
Lipophilic cations such as phosphonium salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in mitochondria in response to the negative inner-transmembrane potentials. Thus, as newly developed noninvasive imaging agents, [F-18]-labeled phosphonium salts may serve as molecular "voltage sensor" probes to investigate the role of mitochondria, particularly in myocardial disease. The present study reports the radiosynthesis of (6-fluorohexyl)triphenylphosphonium salt (3) as a potential agent for myocardial imaging by using positron emission tomography (PET). The reference compound of (6-[F-18]fluorohexyl)triphenylphosphonium salt ([F-18]3) was synthesized with 74% yield via three-step nucleophilic substitution reactions. The reference compound was radiolabeled via two-step nucleophilic substitution reactions of no-carrier-added [F-18]fluoride with the precursor hexane-1,6-diyl bis(4-methylbenzenesulfonate) in the presence of Kryptofix 2.2.2 and K2CO3. The radiolabeled compound was synthesized with 15-20% yield. The radiochemical purity was >98% by analytical HPLC, and the specific activity was >6.10-6.47 TBq/mu mol. The cellular uptake assay showed preferential uptake of [F-18]3 in cardiomyocytes. The results of biodistribution and micro-PET imaging studies of [F-18]3 in mice and rats showed preferential accumulation in the myocardium. The results suggest that this compound would be a promising candidate for myocardial imaging.