^(99m)Tc-HYNIC-siRNA靶向分子探针制备及其在肺腺癌CXCR4 mRNA表达的显像实验研究  

PREPARATION OF ^(99m)Tc-HYNIC-siRNA TARGETING MOLECULAR PROBE AND ITS VALUE IN THE IMAGING OF CXCR4 mRNA EXPRESSION IN LUNG ADENOCARCINOMA

作　　者：赵钰鋆 杨光杰[1] 王振光[1] 龚爱迪 颜蕾 苗文杰 ZHAO Yujun;YANG Guangjie;WANG Zhenguang;GONG Aidi;YAN Lei;MIAO Wenjie(PET/CT Center,The Affiliated Hospital of Qingdao University,Qingdao 266100,China)

机构地区：[1]青岛大学附属医院PET/CT中心,山东青岛266100

出　　处：《精准医学杂志》2019年第1期34-38,共5页Journal of Precision Medicine

基　　金：山东省自然科学基金资助项目(ZR2017MH036);2017年青岛大学医学部"临床医学+x"工程面上项目资助

摘　　要：目的制备基于小干扰RNA(siRNA)的放射性分子探针,探讨其在肺腺癌模型中靶向检测趋化因子受体4(CXCR4)信使RNA(mRNA)的SPECT显像价值。方法以双功能螯合剂肼基烟酰胺(HYNIC)进行^(99m)Tc放射性标记,制备CXCR4 mRNA靶向的干扰组探针及无关序列的对照组探针^(99m)Tc-HYNIC-siRNA,测定标记率、放化纯度及体外稳定性。干扰组及对照组探针经尾静脉注射荷瘤鼠体内(各5只)120min后进行SPECT显像。计算肿瘤与对侧肩部本底放射性摄取比值(T/NT)。显像后处死小鼠,进行肿瘤、肝、肾、脾、心脏、肺体外组织显像。结果成功制备了^(99m)Tc-HYNIC-siRNA探针,干扰组以及对照组的标记率分别为(55.09±2.81)%、(54.38±2.94)%,放化纯度均大于90%。探针在人血清以及生理盐水中120min内可以保持稳定。注射探针后120min SPECT显像可见干扰组肿瘤部位明显放射性浓聚,而对照组肿瘤部位放射性稀疏。干扰组与对照组T/NT比值分别为3.190±0.029、1.153±0.049,差异有显著统计学意义(t=57.68,P<0.01)。体外组织显像同样显示,干扰组肿瘤放射性摄取明显高于对照组肿瘤。结论 ^(99m)Tc-HYNIC-siRNA靶向探针制备简单,在肺腺癌模型中具有靶向CXCR4 mRNA的SPECT显像性能,有望为临床肺癌及其他肿瘤活体内靶基因检测提供有效手段。Objective To prepare a radioactive molecular probe based on small interfering RNA(siRNA),and to investigate its value in the targeted detection of chemokine receptor 4(CXCR4)messenger RNA(mRNA)in lung adenocarcinoma by lung single-photon emission computed tomography(SPECT).Methods The bifunctional chelating agent hydrazinonicotinamide(HYNIC)was used for the radiolabelling of 99m Tc to prepare 99m Tc-HYNIC-siRNA probes targeting CXCR4 mRNA(interference group)and those with unrelated sequences(control group).The labeling efficiency,radiochemical purity,and stability in vitro were measured.The probes in the interference group and the control group were injected into tumor-bearing mice(with 5 mice for each group)via the caudal vein,and SPECT was performed at 120 min after injection.The radioactive uptake ratio of tumor to normal tissue(T/NT)was calculated.The mice were sacrificed after imaging to perform in vitro tissue imaging of tumor,the liver,the kidney,the spleen,the heart,and the lung.Results The 99m Tc-HYNIC-siRNA probes were successfully prepared.The labeling efficiency was(55.09±2.81)%in the interference group and(54.38±2.94)%in the control group,with a radiochemical purity of>90%in both groups.The probes were stable in human serum and normal saline within 120 min.At 120 min after injection,SPECT showed a high radioactive uptake at tumor location in the interference group and a low uptake in the control group.There was a significant difference in T/NT ratio between the interference group and the control group(3.190±0.029 vs 1.153±0.049,t=57.68,P<0.01).In vitro tissue imaging confirmed that the interference group had a significantly higher radioactive uptake of tumors than the control group.Conclusion 99m Tc-HYNIC-siRNA targeting molecular probe is simple to prepare and can help with the targeted imaging of CXCR4 mRNA in lung adenocarcinoma by SPECT.Therefore,it may become an effective method for in vivo target gene detection of lung cancer and other tumors in clinical practice.

关 键 词：肺肿瘤 肿瘤 实验性 RNA 小分子干扰 RNA探针 受体 CXCR4 单光子发射计算机体层摄影术 小鼠 裸 

分 类 号：R734.2[医药卫生—肿瘤] R814.42[医药卫生—临床医学]