Evaluation of (99) (m)TcN-MPO as a new myocardial perfusion imaging agent in normal dogs and in an acute myocardial infarction canine model: comparison with (99) (m)Tc-sestamibi.
Evaluation of (99) (m)TcN-MPO as a new myocardial perfusion imaging agent in normal dogs and in an acute myocardial infarction canine model: comparison with (99) (m)Tc-sestamibi.
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DOI：
10.1007/s11307-010-0304-2
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发表时间：
2011-02
影响因子：
3.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Bu, Lihong;Li, Renfei;Jin, Zhongnan;Wen, Xiaofei;Liu, Shuang;Yang, Baofeng;Shen, Baozhong;Chen, Xiaoyuan
关键词：
99 mTcN-MPO（[99 mTcN（mpo）（PNP 5）]+：mpo=2-巯基吡啶氧化物，PNP 5 = N-乙氧基乙基-N，N-双[2-（双（3-甲氧基丙基）膦基）乙基]胺）是一种阳离子99 mTc-亚硝基配合物，在Sprague道利大鼠体内具有良好的生物分布和心肌摄取，肝脏清除迅速。本研究旨在比较99 mTcN-MPO和99 mTc-Sestamibi在正常犬体内的生物分布和药代动力学，并评价99 mTcN-MPO作为急性心肌梗死犬心肌灌注剂的潜力。5只正常杂种犬静脉注射99 mTcN-MPO。在注射后0.5、1、2、3、4、5、10、20、30、40、60和90 min（p.i.）通过股静脉导管采集静脉血样。在注射后10、20、30、60、90和120 min，通过γ照相机采集前后平面图像。在心脏、肝脏和肺周围绘制感兴趣区域（ROI）。通过将心脏ROI中的平均计数分别除以肝脏和肺ROI中的平均计数来计算心脏/肝脏和心脏/肺比率。为了进行比较，还在相同的5只犬中评价了99 mTc-司他米比。两次检查之间的间隔期为1周，以消除这两种放射性示踪剂之间可能的干扰。此外，在犬梗死模型中，在心肌梗死后24 h，在给予99 mTcN-MPO（n=4）或99 mTc-Sestamibi（n =4）后30和60 min，收集单次正电子发射计算机断层扫描（SPECT）图像。发现99 mTcN-MPO和99 mTc-Sestamibi在p.i. 99 mTcN-MPO和99 mTc-Sestamibi均具有快速的血液清除率，在注射后1分钟时剩余的初始放射性小于50%，在注射后30分钟时剩余的初始放射性小于5%。99 mTcN-MPO和99 mTc-Sestamibi均显示良好的心/肺对比。99 mTcN-MPO的心/肝比值随时间延长而增加（10 min为0.53±0.06，30 min为0.90±0.062，60 min为1.22±0.06），而99 mTc-Sestamibi的心/肝比在所有时间点均保持较低（在10 min时为0.50±0.03，在30 min时为0.64±0.03，在60 min时为0.60±0.02）。犬急性心肌梗塞SPECT显像结果表明，99 mTcN-MPO注射后30 min可显示左室壁和灌注缺损，而99 mTc-Sestamibi注射后显示不明显。99 mTcN-MPO结合了合理的心脏摄取和快速的肝胆排泄，使其成为一种很有前途的心肌灌注显像新示踪剂。
99mTcN-MPO ([99mTcN(mpo)(PNP5)]+: mpo=2-mercaptopyridine oxide and PNP5=N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic 99mTc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of 99mTcN-MPO and 99mTc-Sestamibi in normal dogs, and to evaluate the potential of 99mTcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Five normal mongrel dogs were injected intravenously with 99mTcN-MPO. Venous blood samples were collected via a femoral vein catheter at 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 60, and 90 min post-injection (p.i.). Anterior-posterior planar images were acquired by γ-camera at 10, 20, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around the heart, liver, and lungs. The heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in the liver and lung ROI, respectively. For comparison, 99mTc-sestamibi was also evaluated in the same five dogs. The interval period between the two examinations was 1 week to eliminate possible interference between these two radiotracers. In addition, single positron emission computed tomography (SPECT) images in the canine infarct model were collected 24 h after myocardial infarction at 30 and 60 min after the administration of 99mTcN-MPO (n=4) or 99mTc-Sestamibi (n=4). It was found that 99mTcN-MPO and 99mTc-Sestamibi displayed very similar blood clearance characteristics during the first 90 min p.i. Both 99mTcN-MPO and 99mTc-Sestamibi had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min and less than 5% at 30 min p.i. 99mTcN-MPO and 99mTc-Sestamibi both showed good heart/lung contrast. The heart/liver ratio of 99mTcN-MPO increased with time (0.53±0.06 at 10 min, 0.90±0.062 at 30 min, and 1.22±0.06 at 60 min p.i.), whereas the heart/liver ratio of 99mTc-Sestamibi remained low at all time points (0.50±0.03 at 10 min, 0.64±0.03 at 30 min, and 0.60±0.02 at 60 min p.i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of 99mTcN-MPO but not after 99mTc-Sestamibi. The combination of reasonable heart uptake with rapid hepatobiliary excretion makes 99mTcN-MPO a promising new radiotracer for myocardial perfusion imaging.
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