Kim Young-Seung, Wang Jianjun, Broisat Alexis, Glover David K, Liu Shuang
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
J Nucl Cardiol. 2008 Jul-Aug;15(4):535-46. doi: 10.1016/j.nuclcard.2008.02.022. Epub 2008 Apr 21.
Technetium 99m-N-MPO (Tc-99m-N(mpo)(PNP5)) is a cationic Tc-99m nitrido complex. The objective of this study is to evaluate its potential as a new radiotracer for myocardial perfusion imaging.
Biodistribution studies were performed in Sprague-Dawley rats and guinea pigs to compare the myocardial uptake and excretion kinetics of Tc-99m-N-MPO from noncardiac organs, such as the liver and lungs, with those of the known cationic Tc-99m radiotracers: Tc-99m-N-DBODC5 and Tc-99m-sestamibi. Planar imaging was performed in Sprague-Dawley rats to evaluate the utility of Tc-99m-N-MPO as a myocardial perfusion imaging agent. Metabolism studies were carried out by use of both Sprague-Dawley rats and guinea pigs. In general, the heart uptake of Tc-99m-N-MPO was between that of Tc-99m-sestamibi and Tc-99m-N-DBODC5 over the 2-hour study period. However, the heart-liver ratio of Tc-99m-N-MPO (12.75 +/- 3.34) at 30 minutes after injection was more than twice that of Tc-99m-N-DBODC5 (6.01 +/- 1.45) and approximately 4 times higher than that of Tc-99m-sestamibi (2.90 +/- 0.22). The heart uptake and heart-liver ratio of Tc-99m-N-MPO and Tc-99m-sestamibi in guinea pigs were significantly lower than those obtained in Sprague-Dawley rats. The metabolism studies demonstrated no detectable Tc-99m-N-MPO metabolites in the urine and feces samples of the Sprague-Dawley rats at 120 minutes after injection. In guinea pigs no Tc-99m-N-MPO metabolites were detected in the urine at 120 minutes, but only approximately 60% of Tc-99m-N-MPO remained intact in the feces samples. In contrast, there was no intact Tc-99m-sestamibi detected in urine samples, and less than 15% of Tc-99m-sestamibi remained intact in the feces samples. Planar imaging studies indicated that clinically useful images of the heart may be obtained as early as 15 minutes after injection of Tc-99m-N-MPO.
The combination of favorable organ biodistribution and myocardial uptake with rapid liver clearance makes Tc-99m-N-MPO a very promising myocardial perfusion radiotracer worthy of further evaluation in various preclinical animal models.
锝99m-N-MPO（[Tc-99m-N(mpo)(PNP5)]⁺）是一种阳离子锝99m氮化物络合物。本研究的目的是评估其作为心肌灌注显像新型放射性示踪剂的潜力。
在Sprague-Dawley大鼠和豚鼠中进行生物分布研究，以比较锝99m-N-MPO与已知阳离子锝99m放射性示踪剂（锝99m-N-DBODC5和锝99m-司他米比）从非心脏器官（如肝脏和肺）的心肌摄取和排泄动力学。在Sprague-Dawley大鼠中进行平面显像，以评估锝99m-N-MPO作为心肌灌注显像剂的效用。利用Sprague-Dawley大鼠和豚鼠进行代谢研究。总体而言，在2小时的研究期间，锝99m-N-MPO的心脏摄取量介于锝99m-司他米比和锝99m-N-DBODC5之间。然而，注射后30分钟时，锝99m-N-MPO的心脏-肝脏比值（12.75±3.34）是锝99m-N-DBODC5（6.01±1.45）的两倍多，比锝99m-司他米比（2.90±0.22）高约4倍。豚鼠中锝99m-N-MPO和锝99m-司他米比的心脏摄取量和心脏-肝脏比值显著低于Sprague-Dawley大鼠。代谢研究表明，注射后120分钟时，在Sprague-Dawley大鼠的尿液和粪便样本中未检测到可检测到的锝99m-N-MPO代谢物。在豚鼠中，120分钟时尿液中未检测到锝99m-N-MPO代谢物，但粪便样本中仅约60%的锝99m-N-MPO保持完整。相比之下，尿液样本中未检测到完整的锝99m-司他米比，粪便样本中不到15%的锝99m-司他米比保持完整。平面显像研究表明，注射锝99m-N-MPO后最早15分钟即可获得临床上有用的心脏图像。
良好的器官生物分布、心肌摄取与快速的肝脏清除相结合，使锝99m-N-MPO成为一种非常有前景的心肌灌注放射性示踪剂，值得在各种临床前动物模型中进一步评估。
