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核技术  2015 

99mTc-BAT-AV-45标记的化学动力学研究

DOI: 10.11889/j.0253-3219.2015.hjs.38.010301, PP. 10301-10301

Keywords: 99mTc-BAT-AV-45,标记,阿尔茨海默病,显像剂,化学动力学

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Abstract:

18F-AV-45是近年来研制的一种新型淀粉样多肽(amyloid-?-peptide,A?)蛋白显像剂,能用以诊断阿尔茨海默病(Alzheimer’sDisease,AD)。考虑到我国目前单光子发射计算机断层成像术(Single-PhotonEmissionComputedTomography,SPECT)在临床使用的广泛程度,我们在该分子末端引入BAT双功能螯合基团,成功合成出了BAT-AV-45,用直接法和葡庚糖酸钠(glucoheptonate,GH)配体交换法进行标记以获得高的标记率。使用三种方式进行:(1)同时加BAT-AV-45、GH、99mTc;(2)加BAT-AV-45、99mTc,不加GH;(3)加GH、99mTc,不加BAT-AV-45。分别于4°C、25°C、100°C下反应,并于2min、5min、10min、15min、20min、30min用毛细管取样,用薄层色谱法(ThinLayerChromatography,TLC)测定标记率。反应级数n、速率常数k、平均反应活化能Ea、半衰期t1/2用自编的化学动力学软件进行计算。结果表明,99mTc-BAT-AV-45的直接和配体交换法的标记率与反应温度和反应时间成正比,但直接法的最高标记率仅为3.45%±0.05%,而配体交换法的最高标记率为93.81%±0.91%。计算所得化学动力学参数如下:反应级数n均为1;速率常数k在反应温度4°C、25°C和100°C时,直接法分别为2.00×10?4min?1、3.00×10?4min?1和1.40×10?3min?1;配体交换法分别为0.108min?1、0.115min?1和0.265min?1。平均反应活化能Ea,直接法为17.11kJ?mol?1,配体交换法为6.84kJ?mol?1。半衰期t1/2在4°C、25°C和100°C时,直接法分别为3890.60min、2779.51min和481.39min;配体交换法分别为6.43min、6.00min和2.62min。研究结果表明,利用配体交换法以减低标记反应的活化能,使标记反应易于快速进行,有利于获得高标记率的99mTc-BAT-AV-45。

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