In vitro characterization of 211 At-labeled antibody A33--a potential therapeutic agent against metastatic colorectal carcinoma.
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 (211)At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the (211)At-benzoate-A33 conjugate ((211)At-A33) were investigated and found to be similar to those of (125)I-benzoate-A33 ((125)I-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 (211)At-A33 and (125)I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of (211)At-A33 was also confirmed. After incubation with (211)At-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 (211)At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.
Almqvist
Ylva
Y
Department of Oncology, Radiology, and Clinical Immunology, Uppsala University, Uppsala, Sweden. Ylva.Almqvist@radiol.uu.se
Orlova
Anna
A
Sjöström
Anna
A
Jensen
Holger J
HJ
Lundqvist
Hans
H
Sundin
Anders
A
Tolmachev
Vladimir
V
D000911:Antibodies, Monoclonal / Q000737:chemistry; D000912:Antibodies, Neoplasm / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000737:chemistry; D001246:Astatine / Q000378:metabolism; D002277:Carcinoma / Q000276:immunology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000737:chemistry*; D009362:Neoplasm Metastasis; D011485:Protein Binding; D016499:Radioimmunotherapy / Q000379:methods; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104258:GPA33 protein, human; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D001246:Astatine