Journal
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
Volume 20, Issue 5, Pages 514-523Publisher
MARY ANN LIEBERT INC
DOI: 10.1089/cbr.2005.20.514
Keywords
A33 antigen; monoclonal antibody; At-211; colorectal cancer; radioimmunotherapy
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The humanized antibody A33 binds to the A33 antigen, expressed in 95% of primary and metastatic colorectal carcinomas. The restricted pattern of expression in normal tissue makes this antigen a possible target for radioimmunotherapy of colorectal micrometastases. In this study, the A33 antibody was labeled with the therapeutic nuclide At-211 using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the At-211-benzoate-A33 conjugate (At-211-A33) were investigated and found to be similar to those of I-125-benzoate-A33 (I-125-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (K-d = 1.7 +/- 0.2 nM, and 1.8 +/- 0.1 nM for At-211-A33 and I-125-A33, respectively), and both showed good intracellular retention (70% Of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of At-211-A33 was also confirmed. After incubation with 211At-A33, SW1222 cells had a survival of approximately 0.3% when exposed to some 150 decays per cell (DPC). The cytotoxic effect was found to be dose-dependent, as cells exposed to only 56 DPC had a survival of approximately 5%. The At-211-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.
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