Transition metal chemistry of main group hydrazides, part 14: Evaluation of new Tc-99m chelates of thiol functionalized phosphorus hydrazides

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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 monohydrazides [(MeO) 2P(S)NMeNHCH 2C 6H 4SH], SL1 and [(MeO) 2P(S)NMeNHC(O)C 6H 4SH], SL2 were synthesized and their complexation properties with Re(V) and Tc-99m have been studied. Neutral-lipophilic Tc-99m chelates with both SL1 and SL2 were formed in high yields (95–97%) as a single species ascertained by electrophoresis and reversed-phase HPLC. Biodistribution studies show good in vivo stability and primary clearance of both 99mTc chelates is via the hepatobiliary pathway. Re(V) complexes with SL1 and SL2 were also synthesized using the ReOCl 3(PPh 3) 2 precursor 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 ligands 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 complexes of SL1 and SL2 indicate the potential hydrazido-thiols hold for use as a basis in formulating new Tc-99m radiopharmaceuticals, particularly when thiol moieties are used in conjunction with multi-functional phosphorous hydrazide compounds.