THE SYNTHESIS AND IN-VITRO EVALUATION OF A (99M)TECHNETIUM-NITROIMIDAZOLE COMPLEX BASED ON A BIS(AMINE-PHENOL) LIGAND - COMPARISON TO BMS-181321

We have developed a (99m)Technetium complex for imaging of hypoxic tis sue (BMS-181321). Recently, another nitroimidazole derivative, based u pon a bis(amine-phenol) ligand, was described in the patent literature . To compare this compound to BMS-181321, we have synthesized the liga nd, prepared its Tc-99m complex, and evaluated its performance in two in vitro assays of bioefficacy: membrane permeability and uptake in no rmoxic and anoxic cardiocytes. In attempting to reproduce the synthesi s of the ligand described in the patent application, we found that one intermediate could not be made by the method described, and alternati ve routes were investigated. Complexation of the bis(amine-phenol) nit roimidazole with Tc-99m gave an apparent single complex; this appeared as a broad peak on HPLC analysis. Purification by a solid-phase metho d gave a complex with 95% radiochemical purity. This complex was not p ermeable to cultured bovine brain endothelial cells nor did it show pr eferential uptake in anoxic myocytes.