Use of isothiocyanatobenzyl-DTPA derivatized monoclonal antimyosin Fab for enhanced in vivo target localization

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 {sup 201}Tl (0.6 mCi) distribution in nine animals. Each animal was injected intravenously with 0.5 mCi of {sup 111}In-SCN-DTPA AM-Fab preparations (Prep 1 (n = 5) and 2 (n = 4)). The biodistribution was compared to that of {sup 111}In-labeled conventional bicyclic anhydride DTPA-AM-Fab (n = 5). {sup 111}In-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 {sup 111}In-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 {sup 111}In-labeled AM-Fab in future clinical studies.