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氟-18抗肌球蛋白单克隆抗体片段:犬心肌梗死模型的初步研究

Fluorine-18-antimyosin monoclonal antibody fragments: preliminary investigations in a canine myocardial infarct model.

作者信息

Zalutsky M R, Garg P K, Johnson S H, Utsunomiya H, Coleman R E

机构信息

Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.

出版信息

J Nucl Med. 1992 Apr;33(4):575-80.

PMID:1552343
Abstract

The purpose of this study was to determine in a canine model whether selective myocardial infarct uptake of 18F-labeled antimyosin monoclonal antibody fragments could be achieved in a time frame compatible with the short half-life of this nuclide. Antimyosin monoclonal antibody fragments were labeled with 18F using a succinimidyl [18F]fluorobenzylamine ester acylation agent. Six dogs had myocardial infarction induced by coronary artery occlusion and were reperfused prior to the intravenous administration of 0.6-4.7 mCi of 18F-labeled F(ab')2 (two dogs) or Fab (four dogs). Analysis of tissues obtained 2-4 hr after antibody administration revealed infarct:normal myocardium uptake ratios as high as 14-21:1 for F(ab')2 and 9-12:1 for Fab. Even with Fab, however, prolonged 18F activity in the blood pool interfered with delineation of infarcts by PET imaging. In one dog, perfusion imaging with [13N]ammonia before antimyosin administration was performed, and regions of normal and ischemic myocardium were determined. With these regions of interest, infarct:normal myocardium uptake ratios calculated from the 18F-labeled Fab images increased from 1.5:1 at 1 hr to 4.0:1 at 5 hr. We conclude that 18F-labeled antimyosin fragments may be of value for hot-spot imaging of damaged myocardium with PET; however, blood-pool subtraction techniques will probably be required.

摘要

本研究的目的是在犬模型中确定,在与该核素短半衰期相适应的时间范围内,能否实现18F标记的抗肌球蛋白单克隆抗体片段在选择性心肌梗死部位的摄取。使用琥珀酰亚胺基[18F]氟苄胺酯酰化剂将抗肌球蛋白单克隆抗体片段用18F标记。6只犬通过冠状动脉闭塞诱导心肌梗死,并在静脉注射0.6 - 4.7毫居里的18F标记的F(ab')2(2只犬)或Fab(4只犬)之前进行再灌注。抗体给药后2 - 4小时获取的组织分析显示,F(ab')2的梗死心肌与正常心肌摄取比高达14 - 21:1,Fab为9 - 12:1。然而,即使使用Fab,血池中的18F活性持续时间较长,干扰了PET成像对梗死灶的描绘。在1只犬中,在给予抗肌球蛋白之前用[13N]氨进行灌注成像,并确定正常和缺血心肌区域。利用这些感兴趣区域,从18F标记的Fab图像计算出的梗死心肌与正常心肌摄取比从1小时时的1.5:1增加到5小时时的4.0:1。我们得出结论,18F标记的抗肌球蛋白片段可能对用PET进行受损心肌的热点成像有价值;然而,可能需要血池减法技术。

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