EVALUATION OF A NEW DTPA-DERIVATIVE CHELATOR - COMPARATIVE BIODISTRIBUTION AND IMAGING STUDIES OF IN-111 LABELED B3 MONOCLONAL-ANTIBODY IN ATHYMIC MICE BEARING HUMAN EPIDERMOID CARCINOMA XENOGRAFTS

Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3 conjugated to either the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2-(p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with In-111, were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed by most carcinomas. Both In-111-(CHX-B)-B3 and In-111-(1B4M)-B3 showed good tumor targeting with peak values observed at 72 h with 27.6 +/- 7.6 and 25.4 +/- 1.7% ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and, confirmed by the imaging results. In particular, tumor-to-liver ratios increased from 5.0 +/- 0.9 at 24 h to 9.2 +/- 2.0 at 168 h for In-111-(CHX-B)-B3 and from 4.5 +/- 0.6 to 8.9 +/- 3.5 for In-111-(1B4M)-B3. This was mainly the result of low liver accumulation of both In-111-(CHX-B)-B3 and In-111-(1B4M)-B3, with only 2.48 +/- 0.46 and 2.5 +/- 0.9% ID/g at 168 h, respectively (P > 0.05). Our findings indicate that either CHX-B or 1B4M can be successfully used for In-111-labeling of MAbs and that In-111-B3 may represent a promising radioimmunoimaging agent.