Evaluation of novel cationic 99mTc(I)-tricarbonyl complexes as potential radiotracers for myocardial perfusion imaging
Evaluation of novel cationic 99mTc(I)-tricarbonyl complexes as potential radiotracers for myocardial perfusion imaging
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DOI：
10.1016/j.nucmedbio.2006.08.009
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发表时间：
2006-11-01
影响因子：
3.1
通讯作者：
Liu, Shuang
中科院分区：
文献类型：
--
作者：
He, Zhengjie;Hsieh, Wen-Yuan;Liu, Shuang
本文报道了三种阳离子Te-99 m（I）-三羰基配合物[Te-99 m（CO）（3）（L）]（+）的评价。（L= N-甲氧基乙基-N，N-双[2-（双（3-乙氧基丙基）膦基）乙基]胺（ME-PNP），（双（3-乙氧基丙基）膦基）乙基]胺（15 C5-PNP）和N-[18-冠-6）-2-基]-N，N-双[2-（双（3-乙氧基丙基）膦基）乙基]胺（18 C6-PNP）-作为心肌灌注成像的潜在放射性示踪剂。使用Sprague-Dawley大鼠进行生物分布、成像和代谢研究。结果表明，双膦配体对其阳离子Tc-99 m（I）三羰基配合物的生物分布特性和清除动力学有显著影响。在本研究评价的三种放射性示踪剂中，[Tc-99 m（CO）（3）（15 C5-PNP）]（+）具有非常高的初始心脏摄取，并且在大鼠心肌中保留> 2 h。它还显示出从肝脏和肺部的快速清除。在注射后30分钟，[Te-99 m（CO）（3）（15 C5-PNP）（+）]的心/肝比与Tc-99 m-Sestamibi相似，为后者的2.5倍。[Te-99 m（CO）（3）（15 C5-PNP）]（+）与（TcN）-Tc-99 m-DBODC 5在心脏摄取、心肺比和心脏/肝脏比方面几乎相同。代谢研究结果表明，[Te-99 m（CO）（3）（15 C5-PNP）]（+）在尿液中没有显著代谢，但在注射后120 min，粪便样品的放射性高效液相色谱图中确实显示出一个小的代谢物峰（< 10%）。结果：[Tc-99 m（CO）（3）（15 C5-PNP）]+的肝脏清除率明显优于Tc-99 m-Sestamibi，可在注射后30 min内获得有临床价值的心脏显像。[Tc-99 m（CO）（3）（15 C5-PNP）]（+）是一种非常有前途的候选药物，可在各种动物模型中进行更多的临床前评价。(c)2006年爱思唯尔公司All rights reserved.
This report describes the evaluation of three cationic Te-99m(I)-tricarbonyl complexes - [Te-99m(CO)(3)(L)](+) (L=N-methoxyethyl-N,Nbis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (ME-PNP), N-[15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (15C5-PNP) and N-[18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (18C6-PNP)) - as potential radiotracers for myocardial perfusion imaging. Biodistribution, imaging and metabolism studies were performed using Sprague-Dawley rats. It was found that bisphosphine ligands have a significant impact on the biodistribution characteristics and clearance kinetics of their cationic Tc-99m(I)tricarbonyl complexes. Among the three radiotracers evaluated in this study, [Tc-99m(CO)(3)(15C5-PNP)](+) has a very high initial heart uptake and is retained in the rat myocardium for > 2 h. It also shows rapid clearance from the liver and lungs. The heart/liver ratio of [Te-99m(CO)(3)(15C5-PNP)(+) is similar to 2.5 times better than that of Tc-99m-sestamibi at 30 min postinjection. [Te-99m(CO)(3)(15C5-PNP)](+) is almost identical to (TcN)-Tc-99m-DBODC5 with respect to heart uptake, heart/lung ratio and heart/liver ratio. Results from metabolism studies show that there is no significant metabolism for [Te-99m(CO)(3)(15C5-PNP)](+) in the urine, but it does show a small metabolite peak (< 10%) in the radio high-performance liquid chromatography chromatogram of the feces sample at 120 min postinjection. Results planar imaging studies demonstrate that [Tc-99m(CO)(3)(15C5-PNP)]+ has a much better liver clearance profile than Tc-99m-sestamibi and might give clinically useful images of the heart as early as 30 min postinjection. [Tc-99m(CO)(3)(15C5-PNP)](+) is a very promising candidate for more preclinical evaluations in various animal models. (c) 2006 Elsevier Inc. All rights reserved.