摘要
18F-AV-45是近年来研制的一种新型淀粉样多肽(amyloid-β-peptide,Aβ)蛋白显像剂,能用以诊断阿尔茨海默病(Alzheimer’s Disease,AD)。考虑到我国目前单光子发射计算机断层成像术(Single-Photon Emission Computed Tomography,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2 min、5 min、10 min、15 min、20 min、30 min用毛细管取样,用薄层色谱法(Thin Layer Chromatography,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2.00×10-4 min-1、3.00×10-4 min-1和1.40×10-3 min-1;配体交换法分别为0.108 min-1、0.115 min-1和0.265 min-1。平均反应活化能Ea,直接法为17.11 k J·mol-1,配体交换法为6.84 k J·mol-1。半衰期t1/2在4°C、25°C和100°C时,直接法分别为3 890.60 min、2 779.51 min和481.39 min;配体交换法分别为6.43 min、6.00 min和2.62 min。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。
Background： In recent years, a new amyloid-β-peptide （Aβ） protein imaging agent 18F-AV-45 which can be used to diagnose Alzheimer＇s disease （AD）, was developed. Whereas single-photon emission computed tomography （SPECT） was widely applied in medical clinic in China, a two function compound BAT was connected to the end of AV-45 to successfully synthesize a new compound BAT-AV-45, and its chemical kinetics of labeling reaction with 99mTC was studied. Purpose： 99mTc-BAT-AV-45 was synthesized via direct reaction and ligand exchange for obtaining high labeling yield. Methods： The labeling reactions were performed with three modes： （1） adding BAT-AV-45, GH and 99mTc; （2） adding BAT-AV-45 and 99mTC but non GH; （3） adding GH and 99mTc but non BAT-AV-45. Reactants were incubated at 4 ℃, 25 ℃ and 100 ℃, respectively. Samples were taken with capillary from vials at 2 min, 5 min, 10 min, 20 min and 30 min, respectively. Labeling yields were determined by thin layer chromatography （TLC）. Order of reaction n, rate constant k, average activation energy Ea and reaction half life tl/2 of labeling reaction were calculated with chemical kinetics software compiled by ourselves. Results： The results expressed that the labeling yields of 99mTc-BAT-AV-45 with direct reaction and ligand exchange were proportional to reaction temperature and reaction time. The highest labeling yields with direct reaction and ligand exchange were 3.45%±0.05% and 93.81%±0.91%, respectively. The parameters of chemical kinetics were calculated, n was 1. k were 2.00×10 4 min1, 3.00×10-4 min-1, 1.40×10-3 min-1 with direct reaction and 0.108 min1, 0.115 min-1, 0.265 rain 1 with ligand exchange at 4 ℃, 25 ℃ and 100 ℃, respectively. Ea were 17.11 kJ·mo1-1 with direct reaction and 6.84 kJ·mo1-1 with ligand exchange, respectively, tl/2 were 3 890.60 rain, 2 779.51 min, 481.39 min with direct reaction and 6.43 min, 6.00 min, 2.62 min with ligand exchange at 4 ℃, 25 ℃ and 100 ℃, respectively. Conclusi
出处
《核技术》
CAS
CSCD
北大核心
2015年第1期39-44,共6页
Nuclear Techniques
基金
国家自然科学基金项目(No.81371590)
江苏省自然科学基金项目(No.BK2011167)资助
