In vitro and in vivo characterization of a novel bifunctionalized water-soluble dithia-bisphosphine Tc-99m complex

The novel tetradentate, bifunctional chelating agent (BFCA) Dithia(bishydro xymethyl)bisphosphine (P2S2-COOH) was synthesized. The water-soluble ligand P2S2-COOH produces a Tc-99m-complex of radiochemical purity greater than o r equal to 95% at a BFCA concentration of 10(-5) M by direct reduction of [ (TcO4)-Tc-99m](-) in presence of the ligand with Sn2+ or by trans-chelation using Tc-99m-gluconate. HPLC analyses indicate the formation of a single s pecies. The chromatographic retention time for this new technetium BFCA is similar to the corresponding Re(V)-BFCA, suggesting the identical chemical structure on the tracer level. The Tc-99m-P2S2-COOH complex is stable over a wide range of pH (3-9) for greater than or equal to 24 h. Biodistribution studies in the normal mouse model exhibited a fast clearance of the radioa ctivity from the bloodstream and excretion of the complex through the renal and the hepatobiliary pathways. The results of this investigations suggest that the phosphinethioether P2S2-chelate system is a possible alternative to the other bifunctional systems for the radiolabeling of site specific bi omolecules with Tc-99m and Re-186/188.