靶向生长抑素受体SSTR2的新型白蛋白亲和放射性碘标记分子探针的制备与评价  

Synthesis and evaluation of a novel albumin-binder modified radioiodinated probe for somatostatin receptor SSTR2 targeting

作　　者：林晓茹 方建阳 李靖超 郭志德[1] 张现忠[1] LIN Xiaoru;FANG Jianyang;LI Jingchao;GUO Zhide;ZHANG Xianzhong(State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics,Center for Molecular Imaging and Translational Medicine,School of Public Health,Xiamen University,Xiamen 361102,China)

机构地区：[1]厦门大学公共卫生学院,分子疫苗学和分子诊断学国家重点实验室,分子影像暨转化医学研究中心,福建厦门361102

出　　处：《厦门大学学报（自然科学版）》2022年第1期96-104,共9页Journal of Xiamen University：Natural Science

基　　金：国家自然科学基金(81901805,21976150)。

摘　　要：生长抑素受体亚型2(SSTR2)在神经内分泌肿瘤和多种心血管疾病中高表达,是一个非常有吸引力的靶点.基于铜介导下放射性碘离子与苯硼酸底物发生氧化偶联反应的方法,构建了靶向SSTR2的新型放射性碘标记分子探针[^(131)I]IPBA-TATE和[^(131)I]IBA-TATE(对照),并在体外评价了其理化性质及白蛋白结合特性.在BALB/c小鼠中测定其血液末端清除半衰期,并在正常小鼠和AR42J肿瘤模型小鼠中研究其生物分布特性(以每克组织中摄取注射剂量的百分率(%ID/g)为单位).结果表明:[^(131)I]IPBA-TATE的放射性化学产率为(64.0±4.2)%(n=3),在体外具有良好的稳定性和蛋白亲和性;相比于[^(131)I]IBA-TATE,[^(131)I]IPBA-TATE的血液末端清除半衰期延长了60%,为(25.50±3.35)h.在给药后4 h,[^(131)I]IPBA-TATE在AR42J肿瘤中的摄取为(1.21±0.67)%ID/g,具有较高的瘤/肉比(5.30±2.07).可见[^(131)I]IPBA-TATE是一种基于奥曲肽的新型碘标记白蛋白亲和探针,有望用于SSTR2阳性肿瘤的单光子发射计算机断层显像及放射性核素靶向治疗.Somatostatin receptor subtype 2(SSTR2)is highly expressed in neuroendocrine tumors and a variety of cardiovascular diseases,making it a very attractive target.In this study,novel radioiodinated[^(131)I]IPBA-TATE and[^(131)I]IBA-TATE(as control)targeting for SSTR2 were obtained with a copper-mediated radioiodination approach using aryl boronic acids,and their physical and chemical properties and albumin-binding properties were determined in vitro.The blood terminal removal half-life and biodistribution(percentage of injected dose per gram tissue(%ID/g))studies of[^(131)I]IPBA-TATE and[^(131)I]IBA-TATE were performed in normal mice and AR42J tumor-bearing model mice.The results showed that the[^(131)I]IPBA-TATE was synthesized in good radiochemical yield of(64.0±4.2)%(n=3),with good stability and albumin-binding property in vitro.The blood terminal removal half-life of[^(131)I]IPBA-TATE was extended by 60%compared with[^(131)I]IBA-TATE,and the value was(25.50±3.35)h.The uptake of[^(131)I]IPBA-TATE in AR42J tumor was(1.21±0.67)%ID/g after 4 h post-injection with a high tumor-to-muscle ratio(5.30±2.07).Accordingly,[^(131)I]IPBA-TATE is a novel radioiodinated probe based on octreotide with protein binder modification,which is expected to be used in single photon emission computed tomography imaging of SSTR2-positive tumors and radionuclide targeted therapy.

关 键 词：生长抑素受体亚型2 奥曲肽衍生物 放射性碘标记 白蛋白亲和探针 

分 类 号：TL923[核科学技术—核燃料循环与材料]