A Novel Ternary Ligand System Useful for Preparation of Cationic 99mTc-Diazenido Complexes and 99mTc-Labeling of Small Biomolecules
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- 作者：Young-Seung Kim ; Zhengjie He ; Wen-Yuan Hsieh ; and Shuang Liu
- 刊名：Bioconjugate Chemistry
- 出版年：2006
- 出版时间：March 2006
- 年：2006
- 卷：17
- 期：2
- 页码：473 - 484
- 全文大小：225K
- 年卷期：v.17,no.2(March 2006)
- ISSN：1520-4812
文摘
This report describes a novel ternary ligand system composed of a phenylhydrazine, a crown ether-containingdithiocarbamate (DTC), and a PNP-type bisphosphine (PNP). The combination of three different ligands with99mTc results in cationic 99mTc-diazenido complexes, [99mTc(NNAr)(DTC)(PNP)]+, with potential radiopharmaceuticals for heart imaging. Synthesis of cationic 99mTc-diazenido complexes can be accomplished in two steps.For example, the reaction of phenylhydrazine with 99mTcO4- at 100 
C in the presence of excess stannous chlorideand 1,2-diaminopropane-N,N,N',N'-tetraacetic acid (PDTA) results in the [99mTc(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 C for 15 min to give the complex, [99mTc(NNPh)(L4)(PNP6)]+ in high yield (>90%). Cationic complexes [99mTc(NNPh)(DTC)(PNP)]+ are stable for 
6 h. Theircomposition was determined to be 1:1:1:1 for Tc:NNPh:DTC:PNP using the mixed-ligand experiments on thetracer (99mTc) 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 theircationic 99mTc-diazenido complexes. Results from a 99mTc-labeling efficiency experiment showed that 4-hydrazinobenzoic acid (HYBA) might be useful as a bifunctional coupling agent for 99mTc-labeling of small biomolecules.However, the 99mTc-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.
C in the presence of excess stannous chlorideand 1,2-diaminopropane-N,N,N',N'-tetraacetic acid (PDTA) results in the [99mTc(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 C for 15 min to give the complex, [99mTc(NNPh)(L4)(PNP6)]+ in high yield (>90%). Cationic complexes [99mTc(NNPh)(DTC)(PNP)]+ are stable for 6 h. Theircomposition was determined to be 1:1:1:1 for Tc:NNPh:DTC:PNP using the mixed-ligand experiments on thetracer (99mTc) 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 theircationic 99mTc-diazenido complexes. Results from a 99mTc-labeling efficiency experiment showed that 4-hydrazinobenzoic acid (HYBA) might be useful as a bifunctional coupling agent for 99mTc-labeling of small biomolecules.However, the 99mTc-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.