Evaluation of a new DTPA-derivative chelator: Comparative biodistribution and imaging studies of 111In-labeled B3 monoclonal antibody in athymic mice bearing human epidermoid carcinoma xenografts

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Abstract

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-(lB4M)-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-(lB4M)-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.

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    Present address: Department of Nuclear Medicine, National Cancer Institute, F. “G. Pascale”, Via M. Semmola, 80131 Naples, Italy.

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