Practical RE 186 Labeled Products for Radioimmunotherapy

Our ultimate goal is to develop a readily usable rhenium-186-labeled monoclonal antibodyproduct for radioimmunotherapy of colorectal and other types of cancer. Rhenium-186 (t1/2=90h) hasbeta-emissions at 1.07 meV and 0.93 MeV, and imageable gamma-emission (9% abundance) at 137KeV. The Phase-I research will involve preparation of chelator-linked conjugates of a high-affinityCEA-specific antibody, single-vial formulations of the same with tin, and demonstration of expeditiousand sit-specific labeling with rhenium-186 perrhenate. Biodistributions of these radioimmunoconjugatesin tumor-bearing mice will be determined. We will produce a lyophilized antibody preparation which canbe labeled, in one step, to obtain a radioimmunoconjugate with high immunoreactivity, and an in vivoretention resembling that of iodinated antibody. A product fulfilling these criteria will be easily usablein hospital settings, and commercially viable. Initial labeling experiments will be carried out usingrhenium-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 IIprogram.