In vitro characterization of 211 At-labeled antibody A33: a potential therapeutic agent against metastatic colorectal carcinoma
2005 (English)In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 20, no 5, 514-523 p.Article in journal (Refereed) Published
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 211At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the 211At-benzoate-A33 conjugate (211At-A33) were investigated and found to be similar to those of 125I-benzoate-A33 (125I-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (Kd = 1.7 ± 0.2 nM, and 1.8 ± 0.1 nM for 211At-A33 and 125I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of 211At-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 211At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.
Place, publisher, year, edition, pages
2005. Vol. 20, no 5, 514-523 p.
Radiology, Nuclear Medicine and Medical Imaging
IdentifiersURN: urn:nbn:se:uu:diva-104544DOI: 10.1089/cbr.2005.20.514PubMedID: 16248767OAI: oai:DiVA.org:uu-104544DiVA: diva2:219923