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Development of a two‐antibody model for the evaluation of copper‐64 radioimmunotherapy
Author(s) -
Bryan J. N.,
Lewis M. R.,
Henry C. J.,
Owen N. K.,
Zhang J.,
Mohsin H.,
Jia F.,
Sivaguru G.,
Anderson C. J.
Publication year - 2004
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/j.1476-5810.2004.00041.x
Subject(s) - radioimmunotherapy , monoclonal antibody , cytotoxicity , cancer research , internalization , conjugate , antibody , ionizing radiation , chemistry , in vivo , medicine , in vitro , immunology , biochemistry , cell , biology , irradiation , mathematical analysis , physics , mathematics , microbiology and biotechnology , nuclear physics
Abstract Copper‐64 emits β + and β – particles suitable for positron emission tomography and radioimmunotherapy (RIT) of cancer. Copper‐64‐labelled antibodies have caused complete responses in laboratory animal RIT studies at far lower radiation doses than traditionally prescribed. The intracellular localization of copper radioisotopes may lead to cytotoxic effects by mechanisms beyond ionizing radiation damage. The purpose of this research was to develop a model using both internalizing and non‐internalizing antibodies for direct comparison in future RIT studies using the same animal model of cancer. The monoclonal antibodies, cBR96 and cT84.66, were conjugated with N ‐hydroxysulfosuccinimidyl DOTA. All conjugates retained high immunoreactivity and labelled efficiently with 64 Cu with high specific activity and radiochemical purity. Twenty‐four hour biodistributions determined in LS174T tumour‐bearing nude mice demonstrated low organ and high tumour uptakes for both monoclonal antibodies. This model constitutes a promising system for elucidating whether internalization of 64 Cu is responsible for an enhanced tumour cytotoxicity in vivo .