Preclinical evaluation of 177Lu-Nimotuzumab: A potential tool for radioimmunotherapy of epidermal growth factor receptor-overexpressing tumors

Denis Rolando Beckford Vera, Sebastian Eigner, Milos Beran, Katerina Eigner Henke, Alice Laznickova, Milan Laznicek, Frantisek Melichar, Marco Chinol

Research output: Contribution to journalArticle

Abstract

Background: The humanized monoclonal antibody Nimotuzumab (h-R3) has demonstrated an exceptional and better clinical profile than other monoclonal antibodies for immunotherapy of epidermal growth factor receptor-overexpressing tumors. This work deals with the preparation and radiolabeling optimization of 177Lu-Nimotuzumab and their preclinical evaluation. Methods: Nimotuzumab was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10- tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), testing different molar ratios. The immunoconjugates were characterized. The radiolabeling with 177Lu was optimized. Radioimmunoconjugates stability was tested in 2-[bis[2-[bis(carboxymethyl)amino]ethyl]amino]acetic acid (DTPA) excess and human serum. In vitro studies were performed in tumor model cell lines. Receptor-specific binding was tested by competitive inhibition. 177Lu-Nimotuzumab in vivo studies were conducted in healthy and xenograft animals. Results: Nimotuzumab conjugates were obtained with high purity. Radiolabeling yield and specific activities ranged from 63.6% to 94.5% and from 748 to 1142 MBq/mg, respectively. The stability in DTPA excess and human serum was 95.9% and 93.2% after 10 days, respectively. The radioimmunoconjugate showed specific receptor binding in tumor cell lines. Biodistribution in healthy animals showed the typical behavior of the immunoconjugates based on monoclonal antibodies. The study in xenografts mice demonstrated uptake of 177Lu-Nimotuzumab in the tumor and reticuloendothelial organs. Conclusions: 177Lu-Nimotuzumab was obtained with high purity and specific activities under optimal conditions without significant loss in immunoreactivity and might be a potential radioimmunoconjugate for radioimmunotherapy of tumors with epidermal growth factor receptor overexpression.

Original languageEnglish
Pages (from-to)287-297
Number of pages11
JournalCancer Biotherapy and Radiopharmaceuticals
Volume26
Issue number3
DOIs
Publication statusPublished - Jun 1 2011

Keywords

  • Lu
  • EGFR
  • h-R3
  • monoclonal antibodies
  • Nimotuzumab
  • radioimmunotherapy
  • radiolabeling

ASJC Scopus subject areas

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

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