摘要
目的:寻找具有合适化学交换位点的小分子化合物作为磁共振对比剂并探讨其CEST特性和潜在应用价值.方法:初步筛选18种小分子化合物,通过磷酸盐缓冲液制备成试管模型.利用7.0 T磁共振成像仪上的CEST序列进行数据采集.利用MATLAB平台上工程师编辑的程序脚本进行数据后处理.采用GraphPad Prism软件中的pearson相关性分析方法对数据结果进行统计学分析.结果:除生物素外,所测试的一系列小分子物质均具有CEST特性.L-苯丙氨酸、盐酸多巴胺和奥沙拉秦钠的最佳化学交换位点分别为2.65 ppm、2.6 ppm和9.8 ppm,CEST效应的大小与饱和能量呈正相关,与pH值呈负相关(P＜0.05).3-硝基-4氨基苯酚和硫普罗宁的化学位移偏移位点分别位于1.65 ppm和-2.5 ppm,其CEST效应的大小与pH值无显著相关性(P＞0.05).2,5-二羟基苯酚和5-氨基水杨酸具有2个化学交换位点,分别为1.8 ppm、8.5 ppm和1.0 ppm、8.0 ppm,最适pH值为6.8.其它小分子物质,如丙烯酰胺(2.75 ppm)、L-半胱氨酸(-2.75 ppm)、内消旋-2,3-二巯基丁二酸(-2.5 ppm)、血卟啉(-12.5 ppm)、水杨酸(9.3 ppm)、环糊精(0.5 ppm)、透明质酸(1.0 ppm)、叶酸(1.8 ppm)、3,5-二羟基苯甲酰胺(1.8 ppm)和谷胱甘肽(-2.75 ppm和3.0 ppm),由于分子结构不同,各自的CEST特性亦不同.结论:我们通过一小群初步筛选的候选物,证明了具有CEST效应的一类小分子化合物具有作为非金属依赖性磁共振对比剂的潜力.水杨酸及其类似物是一类非常理想的外源性CEST对比剂候选物.总之,每种小分子物质都有其独特的CEST特性,未来可以有针对性设计其潜在应用价值.
Abstract
Objective:To investigate some small molecular compounds with an appropriate chemical exchange sites as magnetic resonance contrast agents and explore their CEST characteristics and potential application value.Methods:18 kinds of small molecular substances were selected and dis-solved in phosphate buffered saline(PBS)to prepare phantoms.All images were performed on an Agi-lent 7.0T MR system.An improved version of continuous wave echo planar imaging sequence was used for the CEST imaging.All of the CEST image processing and data analyses were performed using cus-tomwritten scripts in MATLAB.The Pearson correlation analysis method in GraphPadPrism software was used to statistically analyze the data results.Results:Except for biotin,a series of small molecular substances had the characteristics of CEST.The optimal chemical exchange sites of L-phenylalanine,dopamine hydrochloride,and olsalazine sodium were at 2.65ppm,2.6ppm,and 9.8ppm,respectively.The CEST effects of them were positively correlated with the saturated power and negatively correla-ted with the pH value(P＜0.05).The optimal chemical exchange sites for 4-amino-3-nitrophenol and N-(2-Mercaptopropionyl)glycine were at 1.65ppm and-2.5ppm,respectively,and the magnitude of their CEST effect is not related to the pH value.2,5-dihydroxybenzoic acid and 5-aminosalicylic acid both had two chemical exchange sites,which were at 1.8ppm,8.5ppm,1.0ppm,and 8.0ppm,respective-ly.Other small molecular substances,such as acrylamide(2.75ppm),L-cysteine(-2.75ppm),meso-2,3-Dimercaptosuccinic acid(-2.5ppm),Hematoporphyrin(-12.5ppm),salicylic acid(9.3ppm),α-Cy-clodextrin(0.5ppm),Hyaluronic acid(1.0ppm),Folic acid(1.8ppm),3,5-Dihydroxybenzamide(1.8ppm)and Glutathione(-2.75ppm and 3.0ppm),due to the differences of molecular structure,the CEST characteristics were different.Conclusion:From a small group of preliminarily screened candi-dates,we demonstrated a class of small molecules with CEST effect can be used as a nonmetallic MR contrast agent.Salicylic acid and its analogues are a very ideal candidate for exogenous CEST contrast agents.In summary,each small molecule substance has its own unique CEST characteristics,and its potential application value can be targeted and designed in the future.
基金项目
湖北省自然科学基金计划项目资助(2022CFB960)
襄阳市医疗卫生领域科技计划项目(2022YL15A)
襄阳市医疗卫生领域科技计划项目(2022YL19A)
NETL
NSTL
万方数据