PRACTICAL RE 186 LABELED PRODUCTS FOR RADIOIMMUNOTHERAPY

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The ultimate goal of this project is to develop a readily usable rhenium- 186-labeled monoclonal antibody product for radioimmunotherapy of colorectal and other types of cancer. Rhenium-186 (t1/2=90h) has beta- emissions at 1.07 meV and 0.93 MeV, and imageable gamma-emission (9% abundance) at 137 KeV. The Phase-I research will involve preparation of chelator-linked conjugates of a high-affinity CEA-specific antibody, single-vial formulations of the same with tin, and demonstration of expeditious and sit-specific labeling with rhenium-186 perrhenate. Biodistributions of these radioimmunoconjugates in tumor-bearing mice will be determined. The objective is to produce a lyophilized antibody preparation which can be labeled, in one step, to obtain a radioimmunoconjugate with high immunoreactivity, and an in vivo retention resembling that of iodinated antibody. a product fulfilling these criteria will be easily usable in hospital settings, and commercially viable. Initial labeling experiments will be carried out using rhenium- 188 perrhenate, which is readily available from an in-house tungsten- rhenium generator. Extensive animal preclinical studies, and initial clinical studies will be carried out in an SBIR Phase II program.