TWO STEP TC99M IMAGING USING BISPECIFIC ANTIBODIES

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A series of anti-CEA x anti-indium-DTPA (hMN-14 x 734) bispecific antibodies (bsAbs) will be prepared and characterized. These bsAbs will be compared for tumor uptake and clearance pattern in GW-39 tumor bearing mice. The bsAb with the highest tumor uptake and high tumor/non-tumor (T/NT) ratio will be studied further to develop into an imaging system. The tumors will be targeted with the bsAb. After allowing a sufficient time for tumor accretion and a high T/NT ratio, 99m/Tc-IMP-192, will be injected. IMP-192, a peptidyl Tc-chelator, is formulated with excess indium and lyophilized into a single vial for radiolabeling with Tc-99m. Imp-192 contains two DTPA molecules for antibody recognition and clears rapidly from circulation. The dose of the bsAb and the Tc-99m labeled peptide will be optimized for pretargeted imaging. Reduced background is expected with this pretargeted approach. This optimized pretargeted approach will then later be applicable to pretargeted radioimmunotherapy using Re-188 or Re-186 instead of Tc-99m. Re-188 radiolabeling will require reformulation of the peptide. PROPOSED COMMERCIAL APPLICATION: Final product is envisaged as a two-vial imaging kit for the diagnosis of a variety of cancers. The first vial will contain the bispecific antibody to target the tumors. The second vial will contain a lyophilized peptidyl Tc-99m chelator for instant radiolabeling with Tc-99m. For therapy, Tc-99m will be switched to Re-1898 and peptide will be reformulated.