5-羧基荧光素标记A20FMDV2-Gd-DOTA MR探针的制备及其胰腺癌初步成像研究  

Preparation of A20FMDV2-Gd-DOTA MR probe labeled with 5-carboxyfluorescein and the preliminary imaging for pancreatic cancer

作　　者：尹强强 郝利国[1,2] 谷弘谦 齐贵强 王胜朝 YIN Qiangqiang;HAO Liguo;GU Hongqian;QI Guiqiang;WANG Shengchao(Qiqihar Medical University,Qiqihar,Heilongjiang Province 161006,China;Department of Moleculal Imaging,the First Affiliated Hospital of Qiqihar Medical University,Qiqihar,Heilongjiang Province 161042,China)

机构地区：[1]齐齐哈尔医学院,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学院附属第一医院分子影像教研室,黑龙江齐齐哈尔161042

出　　处：《实用放射学杂志》2023年第5期836-840,共5页Journal of Practical Radiology

基　　金：黑龙江省医药卫生科研课题(20210909010355)。

摘　　要：目的制备一种靶向于胰腺癌整合素αvβ6的双模态分子探针,初步研究MRI/荧光双功能成像在胰腺导管腺癌(PDAC)的表现,为探索早期PDAC诊断的新方法提供理论基础和科学依据。方法以1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)为载体,活化后偶联来自口蹄疫病毒蛋白的20个残基的线性肽(A20FMDV2),纯化后得到A20FMDV2-DOTA。然后加入GdCl_(3)·6H_(2)O进行Gd^(3+)的标记,再进一步利用5-羧基荧光素(5-FAM)标记,透析后得到A20FMDV2-Gd-5-FAM。运用动态光散射法检测其水合粒径和Zeta电位,通过MR分析仪进行弛豫率的测定;利用透射电镜(TEM)观察其形态结构;运用3.0T MR观察其体外MRI效果;并评价其体内MRI与荧光双功能成像表现。结果合成的探针平均水动力尺寸(131.2±7.55)nm,Zeta电位(-25.71±2.00)mV,弛豫率23.49 mM^(-1)s^(-1);电镜下观察其无明显聚集现象;随着分子探针浓度的升高,T_(1)信号也逐渐增强;荧光双功能成像与MRI体内成像显示探针具备良好的双模态成像性能。结论A20FMDV2-Gd-5-FAM双模态分子探针性能稳定,T_(1)弛豫率高,MRI/荧光双功能成像表现良好。Objective To synthesis a bimodal molecular probe that targets to integrinαvβ6,preliminary with MRI/fluorescence dual-imaging function and to investigate its performance in early diagnosis of pancreatic ductal adenocarcinoma(PDAC).Methods 1,4,7,10-tetrazacyclododecane 1,4,7,10-tetraaceticacid(DOTA)served as a carrier,and after activation,coupling with a 20-residue linear peptide(N1 AVPNLRGDLQVLAQKVART_(2)0-NH_(2),A20FMDV2)of the viral protein in the foot-and-mouth disease virus,and purification,A20FMDV2-DOTA was obtained.And then GdCl_(3)·6H_(2) O was added for Gd^(3+)labeling,5-FAM was further employed in the above mixture for labeling,and A20FMDV2-Gd-5-FAM was acquired by dialysis.The hydrated particle size and Zeta potential were detected by dynamic light scattering,and the relaxation rate was measured by a MR analyzer.The morphological structure was observed by transmission electron microscope(TEM).The in vitro MRI effect of the probe was observed by 3.0T MR.At the same time,the MRI and fluorescence dua-l imaging function performances in vivo were evaluated.Results The synthesized probe had a average hydrodynamic size of(131.2±7.55)nm,the Zeta potential of(-25.71±2.00)mV,and the relaxation rate of 23.49 mM^(-1) s^(-1).No significant aggregation was observed under electron microscope.With the gradual increase of the molecular probe concentration,the T_(1) signal intensity progressively increased.And in vivo imaging of fluorescence and MRI revealed that the probe had good bimodal imaging performance.Conclusion The A20FMDV2-Gd-5-FAM bimodal molecular probe has stable performance with high T_(1) relaxation rate,and displays well in MRI/fluorescence bimodal imaging.

关 键 词：整合素ΑVΒ6 双模态分子探针 荧光素 胰腺癌 磁共振成像 

分 类 号：R-332[医药卫生] R445.2R735.9