In vitro and in vivo evaluation of structure-stability relationship of 111In- and 67Ga-labeled antibody via 1B4M or C-NOTA chelates

2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (C-NOTA) or 2-(p-isothiocyanatobenzyl) -6-methyl-diethylenetriamine pentaacetic acid (1B4M) was conjugated to monoclonal antibody T101 (IgG2a), radiolabeled with 111 In or 67 Ga and then purified through size-exclusion HPLC. 111 In 1B4M-T101 and 67 Ga C-NOTA-T101 were stable in in vitro serum at 37 °C. In contrast, 111 In C-NOTA-T101 and 67 Ga 1B4M-T101 were unstable. The biodistribution in normal mice reflected the instability of the metal complex; the less-stable 111 In C-NOTA conjugate left less tracer in blood, but more in liver and kidney whereas the less-stable 67 Ga 1B4M conjugate left less tracer in blood, but more in bone. The biodistribution data suggest that the difference shown between the 111 In and 67 Ga conjugates might be mediated by differences in the in vivo chemistry of the metallic ions.