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- Title
Development of a two-antibody model for the evaluation of copper-64 radioimmunotherapy.
- Authors
Bryan, J. N.; Lewis, M. R.; Henry, C. J.; Owen, N. K.; Zhang, J.; Mohsin, H.; Jia, F.; Sivaguru, G.; Anderson, C. J.
- 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 64Cu 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 64Cu is responsible for an enhanced tumour cytotoxicity in vivo.
- Subjects
RADIOIMMUNOTHERAPY; IMMUNOGLOBULINS; POSITRON emission tomography; MEDICAL imaging systems; DIAGNOSTIC imaging; ANIMAL experimentation; RADIOISOTOPES
- Publication
Veterinary & Comparative Oncology, 2004, Vol 2, Issue 2, p82
- ISSN
1476-5810
- Publication type
Article
- DOI
10.1111/j.1476-5810.2004.00041.x