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A two‐antibody model for copper‐64 radioimmunotherapy: biodistributions and tumor dosimetry in a mouse model of cancer
Author(s) -
Bryan J. N.,
Mohsin H.,
Jia F.,
Siegall C. B.,
Anderson C. J.,
Miller W. H.,
Henry C. J.,
Lewis M. R.
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.1476-5810.2004.0045b.x
Subject(s) - radioimmunotherapy , dota , monoclonal antibody , conjugate , antibody , spleen , kidney , dosimetry , chemistry , cancer research , nuclear medicine , medicine , microbiology and biotechnology , immunology , chelation , biology , mathematical analysis , mathematics , organic chemistry
Objectives: We previously presented preliminary data on pilot biodistributions of 64 Cu‐labeled monoclonal antibodies (mAbs). 1 The purpose of the present studies was to obtain comprehensive biodistributions using a two‐antibody model for direct comparison of an internalizing and a non‐internalizing mAb in the same animal model of cancer. These studies will allow evaluation of the efficacies of the two 64 Cu‐labeled mAbs for radioimmunotherapy (RIT) and are part of a larger, ongoing project examining the unusual tumoricidal properties of internalized 64 Cu. Methods: DOTA (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid) was conjugated to an internalizing antibody, cBR96, and a non‐internalizing antibody, cT84.66. Biodistributions of the 64 Cu‐labeled conjugates in nude mice bearing LS174T human colorectal carcinoma xenografts were obtained at time points from 15 min to 48 h. Mouse tumor dosimetry was calculated using a Monte Carlo N‐Particle Transport Code. Results: The 64 Cu‐DOTA‐cBR96 conjugate demonstrated rapid tumor uptake, reaching 20.2% injected dose per gram of tissue (% ID/g) at 3 h and peaking at 35.4% ID/g by 24 h. Tumor accumulation of 64 Cu‐DOTA‐cT84.66 was more gradual, 8.19% ID/g at 3 h (p = 0.002), and reached 43.8% ID/g by 24 h, but maximum uptake was not statistically different from 64 Cu‐DOTA‐cBR96 (p = 0.05). Liver, spleen, and kidney uptakes were statistically similar at 24 h for both conjugates (p = 0.05). Tumor absorbed radiation doses were estimated to be 1128 rad/mCi for 64 Cu‐DOTA‐cBR96 and 1409 rad/mCi for 64 Cu‐DOTA‐cT84.66. Conclusion: The biodistributions and tumor dosimetry of these two radiolabeled antibodies were sufficiently similar for direct comparison of the therapeutic efficacies of internalizing versus non‐internalizing 64 Cu RIT agents in the same animal model of cancer. RIT studies using this two‐antibody model are currently in progress to test the hypothesis that internalization of 64 Cu is necessary for enhanced cytotoxic properties at low tumor absorbed doses.