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- Title
A two-antibody model for copper-64 radioimmunotherapy: biodistributions and tumor dosimetry in a mouse model of cancer.
- Authors
Bryan, J. N.; Mohsin, H.; Jia, F.; Siegall, C. B.; Anderson, C. J.; Miller, W. H.; Henry, C. J.; Lewis, M. R.
- Abstract
We previously presented preliminary data on pilot biodistributions of 64Cu-labeled monoclonal antibodies (mAbs). 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 64Cu-labeled mAbs for radioimmunotherapy (RIT) and are part of a larger, ongoing project examining the unusual tumoricidal properties of internalized 64Cu. 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 64Cu-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. The 64Cu-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 64Cu-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 64Cu-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 64Cu-DOTA-cBR96 and 1409 rad/mCi for 64Cu-DOTA-cT84.66. 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 64Cu 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 64Cu is necessary for enhanced cytotoxic properties at low tumor absorbed doses.
- Subjects
IMMUNOGLOBULINS; TRANSPLANTATION of organs, tissues, etc.; RADIOIMMUNOTHERAPY; RADIOTHERAPY; DRUG dosage; TUMORS
- Publication
Veterinary & Comparative Oncology, 2004, Vol 2, Issue 2, p99
- ISSN
1476-5810
- Publication type
Abstract
- DOI
10.1111/j.1476-5810.2004.00041.x