A20FMDV2-DOTA-Gd磁共振探针的制备和成像性能研究  

Preparation and preliminary imaging study of a20fmdv2-dota-gd magnetic resonance probe

作　　者：尹强强 郝利国 谷弘谦 齐贵强 李靖宇 赵添羽 刘雅楠 李国华 Yin Qiangqiang;Hao Liguo;Gu Hongqian;Qi Guiqiang;Li Jingyu;Zhao Tianyu;Liu Yanan;Li Guohua(Master of Medical Technology,School of Medical Technology,Qiqihar Medical College,Heilongjiang,161006,China;Department of Imaging Equipment and Technology,School of Medical Technology,Qiqihar Medical College,Heilongjiang,161006,China;Radiology Department of the First Affiliated Hospital of Qiqihar Medical College,Qiqihar,Heilongjiang,161042,China)

机构地区：[1]齐齐哈尔医学院医学技术学院,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学院医学技术学院影像设备与技术学教研室,黑龙江齐齐哈尔161006 [3]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：《齐齐哈尔医学院学报》2022年第19期1801-1805,共5页Journal of Qiqihar Medical University

基　　金：黑龙江省卫生健康委2021年医药卫生科研项目(20210909010355)。

摘　　要：目的制备一种可以靶向于胰腺癌整合素αvβ6的磁共振分子探针A20FMDV2-DOTA-Gd,研究其在胰腺导管腺癌的磁共振表现,为探究早期胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)诊测方法提供新的方法和策略。方法以1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraaceticacid,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(N1AVPNLRGDLQVLAQKVART20-NH 2,A20FMDV2),纯化后得到A20FMDV2-DOTA-Gd;运用激光粒度测定仪检测A20FMDV2-DOTA-Gd水合粒径大小和Zeta电位,通过磁共振分析仪测出探针的弛豫率;利用透射电镜(Transmission electron microscopy,TEM)观察其形态结构,并用电感耦合等离子体质谱(Inductively coupled plasma mass spectrometry,ICP-MS)测定钆元素;运用3.0T磁共振观察其体外矢状位成像效果,使用CCK-8检测A20FMDV2-DOTA-Gd的细胞毒性以及体内毒性,用以评估A20FMDV2-DOTA-Gd的生物相容性;并初步检测荷瘤裸鼠的肿瘤区域磁共振成像表现。结果A20FMDV2-DOTA-Gd探针的平均水合粒径为(122.23±2.78)nm,Zeta电位为(-7.26±1.66)mV,弛豫率为19.30mM-1S-1,高于临床常用的钆喷酸葡胺;电镜下可观察到探针的基本形状;随着A20FMDV2-DOTA-Gd分子探针浓度的升高,体外矢状位的T1信号也逐渐增强;该分子探针细胞毒性较低;体内初步成像效果较好。结论A20FMDV2-DOTA-Gd磁共振分子探针基本性能稳定,探针的弛豫率较好,荷瘤裸鼠磁共振体内成像结果初步显示,A20FMDV2-DOTA-Gd在荷载人胰腺癌ASPC-1的肿瘤部位有磁共振信号的明显增强,证明了该磁共振分子探针具有诊测早期胰腺癌的潜在研究价值。Objective To prepare a magnetic resonance molecular probe A20 FMDV2-DOTA-Gdthat can target pancreatic cancer integrin αvβ6,and to study its MRI appearance in pancreatic ductal adenocarcinoma, which provides methods and strategies for the diagnosis and detection of early pancreatic ductal adenocarcinoma(PDAC).Methods 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid(1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’ ’-tetraaceticacid, DOTA)was used as a carrier, and after activation, a 20-residue linear peptide(N1 AVPNLRGDLQVLAQKVART20-NH2,A20 FMDV2)from the FMD virus protein was coupled, and A20 FMDV2-DOTA-Gd was obtained after purification.A20 FMDV2-Gd was detected by laser particle size analyzer.The hydrated particle size and Zeta potential of A20 FMDV2-DOTA-Gd, the relaxation rate of the probe was measured by a magnetic resonance analyzer;its morphological structure was observed by transmission electron microscopy(TEM),inductively coupled plasma mass spectrometry(ICP-MS)was used to determine gadolinium element.3.0 T magnetic resonance imaging was used to observe the in vitro sagittal imaging effect;using CCK-8 to detect the cytotoxicity and in vivo toxicity of A20 FMDV2-DOTA-Gd to evaluate the bio-compatibility of A20 FMDV2-DOTA-Gd.The magnetic resonance imaging performance of tumor region in tumor-bearing nude mice was preliminarily detected.Results The average hydrated particle size of the A20 FMDV2-DOTA-Gd probe is(122.23±2.78)nm,the Zeta potential is(-7.26±1.66)mV,and the relaxation rate is 19.30mM-1S-1,which were higher than those of the commonly used Aadobenate Dimeglumine.The basic shape of the probe can be observed under the electron microscope.With the increase of the concentration of the A20FMDV2-DOTA-Gd molecular probe,the T1 signal in the sagittal position in vitro is gradually enhanced.The molecular probe performs low cytotoxicity and wellin vivo initial imaging.Conclusions The A20FMDV2-DOTA-Gd magnetic resonance molecular probe has stable basic performance and good relaxation rate

关 键 词：胰腺导管腺癌 磁共振分子探针 弛豫率 整合素ΑVΒ6 

分 类 号：R445.2[医药卫生—影像医学与核医学]