In vitro and in vivo characterization of novel water-soluble dithio-bisphosphine 99mTc complexes.

The water-soluble dithio-bis(hydroxymethyl)phosphine ligands (HOH2C)2P(CH2)2 S(CH2)3S(CH2)2P(CH2OH)2 and (HOH2C)2P(CH2)3S(CH2)3S(CH2)3P(CH2OH)2 were complexed with 99mTc. The 99mTc-P2S2 complexes were formed in high radiochemical purity by simple mixing of 99mTcO-4 with the ligands or by transchelation from 99mTc-citrate. The 99mTc-P2S2 complexes were stable over a wide range of pHs and did not undergo in vitro decomposition for < or = 24 h. High performance liquid chromatographic analysis indicated the formation of singular chemical species. Retention times for each of the new 99mTc-P2S2 complexes are identical to those of corresponding Re(V) complexes, suggesting similar chemical species at the tracer level. Results of this study suggest that the combination of thioether and (hydroxymethyl)phosphine donor centers in new, multidentate ligand frameworks might aid in the development of new bifunctional chelating agents for the use of radiolabeling specific biomolecules.