Development of a simple kit for Tc-99m-MIP-1404, a single amino acid chelate (SAAC II) derived small molecule inhibitor of prostate specific membrane antigen (PSMA) for imaging prostate cancer

523 Objectives The optimization of a simple kit capable of achieving >90% radiochemical purity (RCP) and a specific activity (SA) of >1000 mCi / µmol for the preparation of Tc-99m-MIP-1404 ((7S,12S,16S)-1-(1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)-9,14-dioxo-2,8,13,15-tetraazaoctadecane-7,12,16,18-tetracarboxylic acid)technetium-99m tricarbonyl complex), a novel glutamate-urea-glutamate-derived small molecule inhibitor of PSMA for the detection of metastatic prostate cancer was explored. Methods Radiolabeling of MIP-1404 as a single vial kit was achieved from the intermediate [99mTc(CO)3(H2O)3]+. Optimization of the radiolabeling reaction conditions (time, temperature and concentration) of the final product was undertaken. Radiochemical yield (RCY), RCP, and SA were determined by reverse phase HPLC analysis. Bioanalytical methods were developed for determination of protein binding and plasma stability. Results Radiosynthesis of Tc-99m-MIP-1404 was achieved with a RCY >85% and RCP >92% on a 200 mCi scale. Heating MIP-1404 (100 μg) at 100°C for 60 minutes produced the desired drug product Tc-99m-MIP-1404 with a SA of >2000 mCi / μmol. The single vial kit was shown to be robust and tolerant to concentration and volume changes. The Tc-99m-MIP-1404 demonstrated modest protein binding (32%) and excellent stability, >90% RCP after >24h at room temperature. Conclusions Optimization of a single vial radiolabeling process for the preparation of Tc-99m-MIP-1404 yielded the desired final drug product in high RCY, RCP and SA. This procedure has produced sterile, safe and high quality single vial kit formulations of the Tc-99m-MIP-1404 complex that maintain PSMA selectivity and affords vivid diagnostic images of prostate cancer in early clinical trials