A novel ternary ligand system useful for preparation of cationic (99m)Tc-diazenido complexes and (99m)Tc-labeling of small biomolecules.
This report describes a novel ternary ligand system composed of a phenylhydrazine, a crown ether-containing dithiocarbamate (DTC), and a PNP-type bisphosphine (PNP). The combination of three different ligands with (99m)Tc results in cationic (99m)Tc-diazenido complexes, [(99m)Tc(NNAr)(DTC)(PNP)]+, with potential radiopharmaceuticals for heart imaging. Synthesis of cationic (99m)Tc-diazenido complexes can be accomplished in two steps. For example, the reaction of phenylhydrazine with (99m)TcO4- at 100 degrees C in the presence of excess stannous chloride and 1,2-diaminopropane-N,N,N',N'-tetraacetic acid (PDTA) results in the [(99m)Tc(NNPh)(PDTA)n] intermediate, which then reacts with sodium N-(dithiocarbamato)-2-aminomethyl-15-Crown-5 (L4) and N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]ethoxyethylamine (PNP6) at 100 degrees C for 15 min to give the complex, [(99m)Tc(NNPh)(L4)(PNP6)]+ in high yield (>90%). Cationic complexes [(99m)Tc(NNPh)(DTC)(PNP)]+ are stable for > or = 6 h. Their composition was determined to be 1:1:1:1 for Tc:NNPh:DTC:PNP using the mixed-ligand experiments on the tracer ((99m)Tc) level and was further confirmed by the ESI-MS spectral data of a model compound [Re(NNPh)(L4)(L6)]+. It was found that both DTCs and bisphosphines have a significant impact on the lipophilicity of their cationic (99m)Tc-diazenido complexes. Results from a (99m)Tc-labeling efficiency experiment showed that 4-hydrazinobenzoic acid (HYBA) might be useful as a bifunctional coupling agent for (99m)Tc-labeling of small biomolecules. However, the (99m)Tc-labeling efficiency of HYBA is much lower than that of 6-hydrazinonicotinic acid (HYNIC) with tricine and trisodium triphenylphosphine-3,3',3''-trisulfonate (TPPTS) as coligands.
Department of Industrial and Physical Pharmaceuticals, Division of Nuclear Pharmacy, Purdue University, 575 Stadium Drive, West Lafayette, Indiana 147907-205, USA.
Young-Seung
YS
Kim
Zhengjie
Z
He
Wen-Yuan
WY
Hsieh
Shuang
S
Liu
D002412:Cations / Q000737:chemistry*; D043844:Crown Ethers / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry; D010659:Phenylhydrazines / Q000737:chemistry; D010720:Phosphines / Q000737:chemistry; D013667:Technetium / Q000737:chemistry*; D013859:Thiocarbamates / Q000737:chemistry
D002412:Cations; D043844:Crown Ethers; D008024:Ligands; D015609:Organotechnetium Compounds; D016877:Oxidants; D010659:Phenylhydrazines; D010720:Phosphines; D013859:Thiocarbamates; C030299:phenylhydrazine; D013667:Technetium; C044646:phosphine