Shan Liang
National Center for Biotechnology Information, NLM, NIH
Tri-methoxy-tris-pyrazolyl-Tc-(CO), abbreviated as Tc-TMEOP, is a radiotracer synthesized by Goethals et al. for myocardial perfusion imaging with single-photon emission computed tomography (SPECT) or planar imaging (1). Myocardial perfusion imaging is widely used to assess the blood flow to myocardium during periods of exercise (or stress) and rest (3-5). To precisely assess the blood flow, diverse compounds labeled with various radionuclides have been synthesized and tested in animals and in the clinic (2, 6). Basically, two major issues have to be considered when designing a radiotracer for perfusion imaging. The first issues to be considered are the flow-extraction rate and heart uptake (1, 2). The first-pass myocardial extraction fraction and heart uptake should be high enough to produce a strong signal for myocardial imaging. Both parameters are also essential to obtain high heart/liver, heart/lung, and heart/blood signal ratios at the early time point after injection of the radiotracers. Currently, most radiotracers are labeled with Tc, have a first-pass extraction fraction from 29% to 90%, show a heart uptake from 1% to 3% injected dose (ID), and display a myocardial signal proportional to the regional myocardial blood flow (2). However, some tracers can underestimate the blood flow in the high flow ranges (>2 mL.g−·min−) and overestimate the blood flow in the low flow ranges (<0.2 mL.g−·min−) (2, 4). The second issues to be considered are the liver uptake and clearance, which can significantly influence the diagnostic specificity of myocardial ischemia. Unfortunately, most Tc-labeled radiotracers suffer from high liver uptake with slow clearance, which leads to a high percentage of false-positive or negative results for myocardial ischemia, especially for ischemia in the inferior wall of heart (1). Stimulating patients by eating fatty food before imaging can reduce the liver signal, but the results can vary significantly between individual patients. An optimal radiotracer should have less liver uptake but fast clearance from liver. To overcome the problem of high liver uptake, Goethals et al. synthesized a new radiotracer, Tc-TMEOP, based on tri-carbonyl chemistry (1). TMEOP is a neutral and tridentate nitrogen donor chelator that forms a moderately lipophilic cationic complex upon reaction with the organometallic precursor fac-[Tc(OH)(CO)]. The investigators evaluated the in vitro properties and in vivo pharmacokinetics of Tc-TMEOP and compared them with the data obtained with Tc-sestamibi and Tc-tetrofosmin, two radiotracers approved for clinical use by the United States Food and Drug Administration (1). The results showed that Tc-TMEOP uptake in the heart was between those of Tc-sestamibi and Tc-tetrofosmin, but Tc-TMEOP exhibited a faster liver washout (1). This chapter summarizes the data obtained with Tc-TMEOP.
三甲氧基三吡唑基锝（CO），简称为Tc-TMEOP，是由戈瑟尔斯等人合成的一种放射性示踪剂，用于单光子发射计算机断层扫描（SPECT）或平面成像的心肌灌注显像（1）。心肌灌注显像广泛用于评估运动（或应激）和静息期间心肌的血流情况（3-5）。为了精确评估血流，已合成了多种用不同放射性核素标记的化合物，并在动物和临床中进行了测试（2, 6）。基本上，在设计用于灌注显像的放射性示踪剂时必须考虑两个主要问题。首先要考虑的问题是血流提取率和心脏摄取（1, 2）。首过心肌提取分数和心脏摄取应足够高，以产生用于心肌显像的强信号。这两个参数对于在注射放射性示踪剂后的早期时间点获得高的心脏/肝脏、心脏/肺和心脏/血液信号比也至关重要。目前，大多数放射性示踪剂用锝标记，首过提取分数为29%至90%，心脏摄取为注射剂量（ID）的1%至3%，并且显示出与局部心肌血流成比例的心肌信号（2）。然而，一些示踪剂在高血流范围（>2 mL·g−1·min−1）可能低估血流，而在低血流范围（<0.2 mL·g−1·min−1）可能高估血流（2, 4）。第二个要考虑的问题是肝脏摄取和清除，这会显著影响心肌缺血的诊断特异性。不幸的是，大多数锝标记的放射性示踪剂肝脏摄取高且清除缓慢，这导致心肌缺血的假阳性或假阴性结果比例很高，特别是对于心脏下壁的缺血（1）。在成像前通过进食高脂肪食物刺激患者可以降低肝脏信号，但个体患者之间的结果可能有很大差异。一种最佳的放射性示踪剂应该肝脏摄取少但从肝脏清除快。为了克服肝脏摄取高的问题，戈瑟尔斯等人基于三羰基化学合成了一种新的放射性示踪剂Tc-TMEOP（1）。TMEOP是一种中性三齿氮供体螯合剂，与有机金属前体fac-[Tc(OH)(CO)3]反应后形成一种中等亲脂性的阳离子络合物。研究人员评估了Tc-TMEOP的体外性质和体内药代动力学，并将其与用锝-司他米比和锝-替曲膦获得的数据进行了比较，这两种放射性示踪剂已被美国食品药品监督管理局批准用于临床（1）。结果表明，Tc-TMEOP在心脏中的摄取介于锝-司他米比和锝-替曲膦之间，但Tc-TMEOP表现出更快的肝脏清除（1）。本章总结了用Tc-TMEOP获得的数据。
