一种caspase-3靶向激活型PET分子探针的制备与表征  

Preparation and Characterization of A Caspase-3 Targeted PET Molecular Probe

作　　者：张理霞 徐梁 李惠蓉 梁蓓蓓 林建国 邱玲[1,2] ZHANG Lixia;XU Liang;LI Huirong;LIANG Beibei;LIN Jianguo;QIU Ling(School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou 325000,China;NHC Key Laboratory of Nuclear Medicine,Jiangsu Key Laboratory of Molecular Nuclear Medicine,Jiangsu Institute of Nuclear Medicine,Wuxi 214063,China)

机构地区：[1]温州医科大学基础医学院,浙江温州325000 [2]江苏省原子医学研究所国家卫生健康委员会核医学重点实验室、江苏省分子核医学重点实验室,江苏无锡214063

出　　处：《合成化学》2023年第3期177-185,共9页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(22076069)。

摘　　要：诱导肿瘤细胞凋亡是多种肿瘤治疗方案的作用机制之一,因此检测肿瘤细胞是否产生凋亡已成为评价肿瘤治疗疗效的一种重要指标。以caspase-3为靶点设计凋亡靶向特异性探针,通过对其表达水平进行监测可以及时评估肿瘤疗效。本研究报道了一种靶向caspase-3的正电子发射断层显像(PET)探针[^(18)F]8。采用简便的固相合成法和点击缩合法合成多肽和前体8,利用^(18)F-^(19)F氟离子交换法进行放射性核素氟-18标记,得到放射化学产率16%和放射化学纯度95%的探针[^(18)F]8。探针[^(18)F]8在PBS和小鼠血清中具有较好的稳定性,脂水分配系数Log P为-1.69±0.01,表明探针亲水性较好。高效的合成方法以及良好的理化性质为探针应用于肿瘤凋亡模型的PET成像研究奠定了良好的基础。Inducing tumor cell apoptosis is one of the action mechanisms for several antitumor therapies.Therefore,detection of tumor cell apoptosis has become an important index to evaluate the therapeutic effect of tumor.Cell apoptosis-specific molecular probe was designed with caspase-3 as the target,and therapeutic efficacy could be timely evaluated by monitoring the expression level of caspase-3.In this study,a positron emission tomography(PET)probe[^(18)F]8 targeting caspase-3 was reported.The polypeptide and precursor 8 were synthesized by simple solid-phase synthesis method and click chemistry method,respectively.The precursor 8 was labeled with ^(18)F using ^(18)F-^(19)F isotope exchange method to obtain the probe[^(18)F]8 with radiochemical yield of 16%and radiochemical purity of 95%.The probe displayed good stability in PBS and mouse serum,and the lipo-hydro partition coefficient(Log P)of the probe was determined to be-1.69±0.01,suggesting that the probe was hydrophilic.The convenient synthesis method and good physicochemical properties provided a good basis for the application of the probe in PET imaging of tumor apoptosis.

关 键 词：肿瘤凋亡 CASPASE-3 分子探针 正电子发射断层显像 氟-18标记 合成 表征 

分 类 号：R730.44[医药卫生—肿瘤]