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用99mTc标记的葡萄糖醛酸对急性实验性非再灌注心肌梗死进行极早期无创检测。

Very early noninvasive detection of acute experimental nonreperfused myocardial infarction with 99mTc-labeled glucarate.

作者信息

Narula J, Petrov A, Pak K Y, Lister B C, Khaw B A

机构信息

Center for Drug Targeting and Analysis, Northeastern University, Boston, Mass 02115, USA.

出版信息

Circulation. 1997 Mar 18;95(6):1577-84. doi: 10.1161/01.cir.95.6.1577.

Abstract

BACKGROUND

99mTc glucarate has recently been reported to be an infarct-avid agent. The feasibility of imaging with 99mTc glucarate was evaluated for the early diagnosis of nonreperfused and reperfused myocardial infarction and compared with localization of simultaneously administered 111In anti-myosin.

METHODS AND RESULTS

Four groups of six rabbits each were studied. The left anterior descending coronary artery (LAD) was kept persistently occluded (n = 6) or reperfused after 40 minutes (n = 6) in rabbits. After confirmation of LAD occlusion by 201Tl scintigraphy, a mixture of 99mTc glucarate (15.7 +/- 1.6 mCi) and 111In anti-myosin (0.53 +/- 0.03 mCi) was administered intravenously. Another group of rabbits (n = 6) with 5 or 15 minutes of LAD occlusion were used to assess the affinity of 99mTc glucarate for the ischemic myocardium. The remaining 6 rabbits with reperfused myocardial infarction were used for the assessment of subcellular localization of 99mTc glucarate. 99mTc glucarate cleared rapidly from circulation (elimination t1/2, 36 minutes). Infarcts were visualized within 10 minutes in reperfused and within 30 minutes in nonreperfused coronary territories after intravenous administration. 111In anti-myosin delineated reperfused infarcts within 1 to 3 hours, but no uptake was seen in persistently occluded rabbits. 99mTc glucarate uptake in reperfused and nonreperfused infarct centers was 28 and 12 times greater, respectively, than that in normal myocardium (P = .0001). A direct correlation between glucarate and anti-myosin localization (r = .60 for nonreperfused; 0.76 for reperfused; P < .0001) was observed. Ischemic hearts showed no glucarate uptake. Subcellularly, 99mTc glucarate localized predominantly in the nuclear fraction of the infarct, with lesser extents in the mitochondrial and cytoplasmic fractions.

CONCLUSIONS

Noninvasive imaging of myocardial infarcts with 99mTc glucarate is possible within minutes in persistently occluded or reperfused myocardial infarcts. Early detectability results from the rapid blood clearance and high avidity of glucarate for the acutely necrotic myocardial tissue.

摘要

背景

最近有报道称,99mTc葡糖醛酸是一种梗死灶亲和剂。评估了用99mTc葡糖醛酸成像对未再灌注和再灌注心肌梗死进行早期诊断的可行性,并与同时给予的111In抗肌凝蛋白的定位情况进行了比较。

方法与结果

对四组兔子进行研究,每组6只。在兔子中,左前降支冠状动脉(LAD)持续闭塞(n = 6)或在40分钟后再灌注(n = 6)。通过201Tl闪烁显像确认LAD闭塞后,静脉注射99mTc葡糖醛酸(15.7 +/- 1.6 mCi)和111In抗肌凝蛋白(0.53 +/- 0.03 mCi)的混合物。另一组LAD闭塞5或15分钟的兔子(n = 6)用于评估99mTc葡糖醛酸对缺血心肌的亲和力。其余6只再灌注心肌梗死的兔子用于评估99mTc葡糖醛酸的亚细胞定位。99mTc葡糖醛酸从循环中快速清除(消除半衰期为36分钟)。静脉注射后,在再灌注的冠状动脉区域内10分钟内可观察到梗死灶,在未再灌注的冠状动脉区域内30分钟内可观察到梗死灶。111In抗肌凝蛋白在1至3小时内勾勒出再灌注梗死灶,但在持续闭塞的兔子中未观察到摄取。再灌注和未再灌注梗死中心的99mTc葡糖醛酸摄取分别比正常心肌高28倍和12倍(P = .0001)。观察到葡糖醛酸和抗肌凝蛋白定位之间存在直接相关性(未再灌注时r = .60;再灌注时r = 0.76;P < .0001)。缺血心脏未显示葡糖醛酸摄取。在亚细胞水平上,99mTc葡糖醛酸主要定位于梗死灶的核部分,在线粒体和细胞质部分的定位程度较低。

结论

用99mTc葡糖醛酸对心肌梗死进行无创成像在持续闭塞或再灌注的心肌梗死中数分钟内即可实现。早期可检测性源于葡糖醛酸从血液中的快速清除以及对急性坏死心肌组织的高亲和力。

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