Johnson L L, Schofield L, Mastrofrancesco P, Donahay T, Nott L
Division of Cardiology, Rhode Island Hospital, Providence 02903, USA.
J Nucl Med. 1998 Aug;39(8):1468-75.
Nitroheterocycles are electron affinic, lipophilic compounds that are retained in hypoxic tissue. This study was designed to test the hypothesis that 99mTc-5-oxa-amine-oxime nitroimadazole (BMS-194796) is retained in ischemic myocardial tissue in a swine model of demand ischemia and that the retained tracer can be imaged in vivo.
Eighteen domestic swine were anesthetized, intubated and instrumented, including placement of a stenois (80% narrowing) mounted on a catheter into the left anterior descending (LAD) coronary artery. Twelve experiments had complete sets of data for analysis. Each animal was paced at about 200 bpm for 4 min, and 28 mCi of 99mTc BMS-194796 were injected during the last minute of pacing. Dynamic planar imaging was started after pacing and completed at 2.5 hr. In the last 8 experiments, SPECT imaging was performed after planar imaging and completed 3.5 hr after injection. Hemodynamic measurements were made continuously. Blood flow by microspheres and myocardial lactate extraction were measured at control, during pacing and after 2 hr of recovery. The animals were then killed; the risk region was delineated and the hearts were removed, sliced, imaged and stained with triphenyl tetrazolium chloride.
Nine of the 12 animals became ischemic (net lactate production) during pacing; 3 did not. None of the 3 nonischemic experiments showed focal uptake on ex vivo or in vivo imaging. All 9 of the ischemic experiments showed focal BMS uptake in the risk region on ex vivo imaged slices; 6 of 9 had uptake in the risk region on in vivo imaging; and 4 of these 6 had small scattered areas of subendocardial necrosis in the risk region on triphenyl tetrazolium chloride staining. Four animals had small infarcts in the distribution of proximal LAD branch vessels occluded by the stenosis catheter. All animals with branch vessel infarcts had positive in vivo images. Overall, 8 of 9 ischemic experiments had positive in vivo images.
These data support the conclusion that focal myocardial retention of BMS-194796 can be visualized on in vivo imaging in closed chest large animal model after intravenous injection.
硝基杂环化合物是具有亲电子性、亲脂性的化合物，可滞留在缺氧组织中。本研究旨在验证以下假设：在需求性缺血的猪模型中，99mTc-5-氧杂-胺-肟硝基咪唑（BMS-194796）会滞留在缺血心肌组织中，且滞留的示踪剂能够在体内成像。
18只家猪接受麻醉、插管及仪器植入，包括将一根装有狭窄装置（狭窄80%）的导管置入左前降支（LAD）冠状动脉。12项实验有完整数据集可供分析。每只动物以约200次/分钟的频率起搏4分钟，并在起搏的最后一分钟注射28毫居里的99mTc BMS-194796。起搏后开始动态平面成像，并在2.5小时时完成。在最后8项实验中，平面成像后进行单光子发射计算机断层显像（SPECT）成像，并在注射后3.5小时完成。持续进行血流动力学测量。在对照、起搏期间及恢复2小时后，通过微球测量血流量并测定心肌乳酸摄取量。然后处死动物；划定危险区域，取出心脏，切片，成像并用氯化三苯基四氮唑染色。
12只动物中有9只在起搏期间出现缺血（净乳酸生成）；3只未出现。3项非缺血实验在体外或体内成像中均未显示局灶性摄取。所有9项缺血实验在体外成像切片上均显示危险区域有局灶性BMS摄取；9项中有6项在体内成像时危险区域有摄取；这6项中的4项在氯化三苯基四氮唑染色的危险区域有小的散在性心内膜下坏死区域。4只动物在被狭窄导管阻塞的近端LAD分支血管分布区域有小梗死灶。所有有分支血管梗死的动物体内图像均为阳性。总体而言，9项缺血实验中有8项体内图像为阳性。
这些数据支持以下结论：静脉注射后，在闭合胸腔的大型动物模型中，BMS-194796在心肌中的局灶性滞留可在体内成像中显示出来。
