Mechanism for myocardial localization and rapid liver clearance of Tc-99m-N-MPO: A new perfusion radiotracer for heart imaging
Mechanism for myocardial localization and rapid liver clearance of Tc-99m-N-MPO: A new perfusion radiotracer for heart imaging
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DOI：
10.1007/s12350-009-9068-y
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发表时间：
2009-08-01
影响因子：
2.4
通讯作者：
Liu, Shuang
中科院分区：
文献类型：
--
作者：
Kim, Young-Seung;Shi, Jiyun;Liu, Shuang
[Tc-99 m-N（mpo）（PNP 5）]（+）（Tc-99 m-N-MPO：Hmpo = 2-巯基吡啶N-氧化物，PNP 5 = N-乙氧基乙基-N，N-双[2-（双（3-甲氧基丙基）膦基）乙基]胺）是一种新的用于心肌灌注显像的Tc-99 m放射性示踪剂。本研究的主要目的是通过比较Tc-99 m-N-MPO和Tc-99 m-Sestamibi（[Tc-99 m-（MIBI）（6）]（+）：MIBI = 2-甲氧基-2-甲基丙基异腈）在离体SD大鼠心肌中的亚细胞分布，阐明Tc-99 m-N-MPO和Tc-99 m-Sestamibi的心肌定位和快速肝脏清除机制。在不存在/存在环孢菌素A的情况下，使用SD大鼠进行生物分布和平面成像研究。由于血浆和线粒体电位为负，在线粒体组分中发现84.5% +/- A 3.2%的Tc-99 m-N-MPO，而Tc-99 m-sestamibi为88.0% +/- A 1.5%。它们的线粒体积累没有显著差异。Tc-99 m-N-MPO在大鼠心肌中也能保持其化学完整性。用Cys-A预处理SD大鼠，可显著增加肾脏和肝脏对Tc-99 m-N-MPO的摄取，Tc-99 m-N-MPO和Tc-99 m-Sestamibi的亚细胞分布和定位机制基本一致。肝细胞和肾细胞的MDR转运功能分别负责Tc-99 m-N-MPO从肝和肾的快速清除动力学。Tc-99 m-N-MPO是一种很有前途的心肌灌注放射性示踪剂，具有良好的生物分布特性和快速的肝脏清除率。
[Tc-99m-N(mpo)(PNP5)](+) (Tc-99m-N-MPO: Hmpo = 2-mercaptopyridine N-oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a new Tc-99m radiotracer useful for myocardial perfusion imaging. The main objective of this study is to elucidate the mechanism for myocardial localization and fast liver clearance of Tc-99m-N-MPO in comparison with Tc-99m-sestamibi ([Tc-99m-(MIBI)(6)](+): MIBI = 2-methoxy-2-methylpropylisonitrile).Subcellular distribution of Tc-99m-N-MPO and Tc-99m-sestamibi was examined in the excised Sprague-Dawley (SD) rat myocardium. Biodistribution and planar imaging studies were performed using SD rats in the absence/presence of Cyclosporin-A. Due to negative plasma and mitochondrial potentials, 84.5% +/- A 3.2% of Tc-99m-N-MPO was found in the mitochondrial fraction as compared to 88.0% +/- A 1.5% of Tc-99m-sestamibi. There was no significant difference in their mitochondrial accumulation. Tc-99m-N-MPO was also able to retain its chemical integrity in rat myocardium. Pre-treatment of SD rats with Cys-A result in significant increase in the kidney and liver uptake of Tc-99m-N-MPO.Tc-99m-N-MPO and Tc-99m-sestamibi share almost identical subcellular distribution and localization mechanism. The MDR transport function of hepatocytes and renal cells is responsible for the fast clearance kinetics of Tc-99m-N-MPO from liver and kidneys, respectively. Tc-99m-N-MPO is a very promising myocardial perfusion radiotracer with favorable biodistribution properties and rapid liver clearance.