TRANSITION-METAL CHEMISTRY OF MAIN-GROUP HYDRAZIDES .14. EVALUATION OF NEW TC-99M CHELATES OF THIOL FUNCTIONALIZED PHOSPHORUS HYDRAZIDES

Ligands containing a combination of amine or amide nitrogens and thiol functionalities have been found to form stable chelates with Tc-99m, presumably in oxidation state +5. Two new thio-phosphorus monohydrazid es [(MeO)(2)P(S)NMeNHCH(2)C(6)H(4)SH], SL1 and [(MeO)(2)P(S)NMeNHC(O)C 6H4SH], SL2 were synthesized and their complexation properties with Re (V) and Tc-99m have been studied. Neutral-lipophilic Tc-99m chelates w ith both SL1 and SL2 were formed in high yields (95-97%) as a single s pecies ascertained by electrophoresis and reversed-phase HPLC. Biodist ribution studies show good in vivo stability and primary clearance of both Te-99m chelates is via the hepatobiliary pathway. Re(V) complexes with SL1 and SL2 were also synthesized using the ReOCl3(PPh(3))(2) pr ecursor to obtain the product ReOCl(L)(PPh(3)), where L = SL1 or SL2. H+ was lost from the N-atom and the thiol group in these Re chelates. Even though the Tc-99m chelates of SL1 and SL2 formed at tracer levels are not identical to the Re-chelates (different synthons were used), the Re data suggests complexation of Tc-99m by these hydrazido-thiol l igands will be similar to N,S ligand systems previously used. The good in vitro and in vivo stability and high yields of the Tc-99m complexe s of SL1 and SL2 indicate the potential hydrazido-thiols hold for use as a basis in formulating new Tc-99m radiopharmaceuticals, particularl y when thiol moieties are used in conjunction with multi-functional ph osphorous hydrazide compounds.