Monoclonal antimyosin Fab (AM-Fab) was radiolabeled with 111In via a new bifunctional chelating agent, isothiocyanatobenzyl-DTPA (SCN-DTPA), and used to visualize acute reperfused experimental myocardial infarction. Antibody localization was compared to 201Tl (0.6 mCi) distribution in nine animals. Each animal was injected intravenously with 0.5 mCi of 111In-SCN-DTPA AM-Fab preparations (Prep 1 [n = 5] and 2 [n = 4]). The biodistribution was compared to that of 111In-labeled conventional bicyclic anhydride DTPA-AM-Fab (n = 5). 111In-SCN-DTPA AM-Fab Prep 1 (lowest specific activity) showed highest specific target localization (31.6 +/- 3.5, MEAN infarct[0-20% Tl-201] to normal ration +/- SE) and lowest hepatic sequestration (0.0108 +/- 0.002% ID/g). Prep 2 showed similar infarct localization (18.4 +/- 1.2) to control 111In-DTPA AM-Fab (16.9 +/- 1.1), but had higher hepatic activity (0.0326 +/- 0.014 and 0.0267 +/- 0.006 respectively). This difference in in vivo localization occurred despite the lack of changes in in vitro immunoreactivities of the AM-Fab preparations. The enhanced target localization with minimal hepatic activity may permit a more sensitive diagnostic application of 111In-labeled AM-Fab in future clinical studies.

译文

:单克隆抗肌球蛋白Fab(AM-Fab)通过新型双功能螯合剂异硫氰酸根合苄基-DTPA(SCN-DTPA)进行了放射性标记,并用于可视化急性再灌注实验性心肌梗塞。将抗体的定位与9只动物中201T1(0.6 mCi)的分布进行了比较。给每只动物静脉内注射0.5 mCi的111In-SCN-DTPA AM-Fab制剂(预后1 [n = 5]和2 [n = 4])。将生物分布与111In标记的常规双环酸酐DTPA-AM-Fab(n = 5)进行了比较。 111In-SCN-DTPA AM-Fab Prep 1(最低活性)显示最高特异性靶标定位(31.6 /-3.5,MEAN梗死[0-20%Tl-201]到正常剂量/-SE)和最低的肝螯合(0.0108) /-0.002%ID / g)。制剂2显示出与对照111In-DTPA AM-Fab(16.9 / -1.1)相似的梗塞定位(18.4 / -1.2),但是具有更高的肝活性(分别为0.0326 / -0.014和0.0267 / -0.006)。尽管AM-Fab制剂的体外免疫反应性没有变化,但仍存在体内定位的差异。具有最小的肝活性的增强的靶标定位可以允许在未来的临床研究中更敏感地将111In标记的AM-Fab应用于诊断。

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