Rhenium-188 has favorable physical properties as a therapeutic radionuclide, t-1/2 of 17.0 hr., Emax beta 2.2 MeV, and Egamma 155 keV. Methodology has been developed for conjugation of rhenium in stable complexed form to antibodies. The objective of this proposal is to develop the technology necessary to make high specific activity Re-188 available for radioimmunotherapy using the W-188/Re-188 generator system. This will be done by applying technology used for Mo-99/Tc-99m generators that employs low specific activity Mo-99 and a gel column based on the metal oxide. Tungstein-188 will be prepared at low and high activity levels and various elution parameters studied that affect yield, radionuclidic and chemical purity, and lifetime of use of the radionuclide generator. The study is expected to result in a generator design that will allow production of Re- for animal and clinical evaluation in radiolabeled antibody form for Phase II studies. The technical goals for this Phase I proposal are to demonstrate the feasibility of a generatory system to produce efficiently and repeatedly Re-188 from W-188 in high purity over a useful lifetime, including evaluation of: separation efficiencies; radionuclidic and radiochemical purity; effect of tungsten load; activity dependency; repetitive elution effects; and practical lifetime of use.
