2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic-acid and Carcinoma--Squamous-Cell

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 111In, 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 111In-(CHX-B)-B3 and 111In-(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 111In-(CHX-B)-B3 and from 4.5 +/- 0.6 to 8.9 +/- 3.5 for 111In-(1B4M)-B3. This was mainly the result of low liver accumulation of both 111In-(CHX-B)-B3 and 111In-(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 111In-labeling of MAbs and that 111In-B3 may represent a promising radioimmunoimaging agent.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Chelating Agents; Drug Stability; Female; Humans; Immunotoxins; Indium Radioisotopes; Isothiocyanates; Mice; Mice, Nude; Neoplasm Transplantation; Pentetic Acid; Radionuclide Imaging; Tissue Distribution; Transplantation, Heterologous