In vitro characterization of 211At-labeled antibody A33 - A potential therapeutic agent against metastatic colorectal carcinoma

Ylva Almqvist, Anna Orlova, Anna Sjöström, Holger J. Jensen, Hans Lundqvist, Anders Sundin, Vladimir Tolmachev

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9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)514-523
Number of pages10
JournalCancer Biotherapy and Radiopharmaceuticals
Volume20
Issue number5
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • At
  • A33 antigen
  • Colorectal cancer
  • Monoclonal antibody
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

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