Evaluation of (4-[18F]Fluorophenyl)triphenylphosphonium Ion. A Potential Myocardial Blood Flow Agent for PET
Evaluation of (4-[18F]Fluorophenyl)triphenylphosphonium Ion. A Potential Myocardial Blood Flow Agent for PET
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DOI：
10.1007/s11307-010-0349-2
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发表时间：
2011-06-01
影响因子：
3.1
通讯作者：
Fischman, Alan J.
中科院分区：
文献类型：
--
作者：
Shoup, Timothy M.;Elmaleh, David R.;Fischman, Alan J.
合成了亲油性阳离子化合物(4-[F-18]氟苯基)三苯基膦离子(F-18-FTPP)，并对其作为正电子发射断层扫描(PET)心肌灌注剂进行了评价。在5、30、60min(每个时间点5只大鼠)进行生物分布研究。3只大鼠在注射F-18-FTPP后进行microPET显像。此外，在(NH3)-N-13(111 MBq)和F-18-FTPP(74 MBq)阻断左前降支(LAD)动脉前后，对3只兔进行了microPET显像。在大鼠体内的生物分布数据显示，血液清除迅速，心脏高度蓄积，30min时心血比为75：1。心脏放射性摄取分别为1.64%ID/g、1.51%ID/g和1.57%ID/g。在5、30和60min时，肺活度分别为0.69%ID/g、0.03%ID/g和0.38%ID/g，肝脏摄取率分别为0.34%ID/g、0.18%ID/g和0.17%ID/g，心肺比在5、30和60min时分别为2、5和4。在大鼠和兔体内注射F-18-FTPP后的MicroPET成像显示，心肌活动在最初的峰值对应于血流，然后在1分钟后达到平台期。(NH3)-N-13和F-18-FTPP对正常和LAD闭塞兔的microPET图像的感兴趣区分析表明，这两种示踪剂在正常和病变的血流区域的分布相似。F-18-FTPP在正常和LAD闭塞的兔中的良好心血比及其与(NH3)-N-13分布的相关性表明，这种放射性药物可能作为一种PET试剂来表征线粒体损伤和/或心肌血流。
The lipophilic cationic compound, (4-[F-18]fluorophenyl)triphenylphosphonium ion (F-18-FTPP) was synthesized and evaluated as a potential positron emission tomography (PET) myocardial perfusion agent.F-18-FTPP was prepared from (4-nitrophenyl)triphenylphosphonium nitrate and ammonium [F-18]fluoride by nucleophilic aromatic substitution and was purified by high performance liquid chromatography before use. Biodistribution studies were performed in rats at 5, 30, 60 min (five rats per time point). Three rats were evaluated by microPET imaging after injection of F-18-FTPP. In addition, microPET imaging in rabbits (three) was performed before and after occlusion of the left anterior descending (LAD) artery with (NH3)-N-13 (111 MBq) and F-18-FTPP (74 MBq).Biodistribution data in rats showed rapid blood clearance and high levels of accumulation in the heart; 75:1 heart-to-blood ratio at 30 min. Uptake of radioactivity in the heart was 1.64% ID/G, 1.51% ID/g, and 1.57% ID/g at 5, 30, and 60 min. At 5, 30, and 60 min, lung activity was 0.69% ID/g, 0.03% ID/g, and 0.38% ID/g, and liver uptake was 0.34% ID/g, 0.18% ID/g, and 0.17% ID/g. Heart-to-lung ratios at 5, 30, and 60 min were 2, 5, and 4. Bone accumulation was minimal. MicroPET imaging in both rats and rabbits after injection of F-18-FTPP demonstrated an initial spike of activity in the myocardium corresponding to blood flow followed by a plateau after 1 min. Region of interest analysis of microPET images of normal and LAD-occluded rabbits with (NH3)-N-13 and F-18-FTPP indicated similar distributions of the two tracers in both normal and altered blood flow regions.The excellent heart-to-blood ratio of F-18-FTPP and its correlation with (NH3)-N-13 distribution in normal and LAD-occluded rabbits suggest that this radiopharmaceutical may have potential as a PET agent for characterizing mitochondrial damage and/or myocardial blood flow.