99TcmN(PNP5)(DTC)+混配配合物的合成与小鼠生物分布

Synthesis and Biodistribution in mice of 99TcmN(PNP5)(DTC)+ Heterocomplexes

  • 摘要: 经配体交换反应制备了4种脂溶性阳离子配合物:99TcmN(PNP5)(PODC)+( PNP5: N,N-二二(3-甲氧基丙基)膦基乙基-2-乙氧基乙胺,PODC: N-甲氧基氨荒酸盐)、99TcmN(PNP5)(BODC)+(BODC: N-乙氧基氨荒酸盐)、99TcmN(PNP5)(MOPDTC)+(MOPDTC: N-甲氧基丙基氨荒酸盐)和99TcmN(PNP5)(EOPDTC)+(EOPDTC: N-乙氧基丙基氨荒酸盐),放化纯均大于90%。小鼠生物分布结果显示:4种配合物在小鼠体内均具有不同程度的心肌摄取和滞留,主要经肾排泄,在血、肝和肺等非靶组织中清除较快。其中,99TcmN(PNP5)(EOPDTC)+的靶与非靶组织放射性摄取比(T/NT)较高,30min时,心脏/血、心脏/肺、心脏/肝分别为23.75、3.45、3.63,利于快速心肌显像,若能通过结构修饰提高其心肌摄取,有望发展为一种新型心肌灌注显像剂。

     

    Abstract: In this study, 99TcmN(PNP5)(PODC)+ (PNP5: bis(dimethoxypropylphosphinoethyl)ethoxyethylamine,PODC:N-methoxyethyl dithiocarbamate), 99TcmN(PNP5)(BODC)+(BODC:N-ethoxyethyl dithiocarbamate), 99TcmN(PNP5)(MOPDTC)+ (MOPDTC:N-methoxypropyl dithiocarbamate) and 99TcmN(PNP5)(EOPDTC)+ (EOPDTC: N-ethoxypropyl dithiocarbamate) four new 99Tcm-nitride heterocomplexes were synthesized by ligand exchange reaction. They are lipophilic cations with good stability, and their radiochemical purities are over 90%. Results of biodistribution in mice show that they have different degrees of myocardial uptake and retention, and that the activity of blood, liver, lungs and other non-target tissues washes out rapidly and is mainly eliminated through kidneys. Of four complexes, the heart/blood, heart/lung and heart/liver ratios at 30min of 99TcmN(PNP5)(EOPDTC)+ are 23.75, 3.45, 3.63, in favor of fast cardiac imaging. It could be developed a novel myocardial perfusion imaging agent by structural optimization to improve its myocardial uptake.

     

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