免疫检查点靶向小分子PET探针的制备及表征
Preparation and Characterization of Small-molecule PET Probes Targeting Immune Checkpoints
梁蓓蓓 1李惠蓉 1徐梁 2方晶 2林建国 1邱玲1
作者信息
- 1. 温州医科大学 基础医学院,浙江 温州 325035;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
- 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
- 折叠
摘要
程序性细胞死亡蛋白-1(PD-1)及其配体-1(PD-L1)作为免疫治疗的关键靶点,其表达水平与患者对免疫治疗的应答情况密切相关,准确检测PD-L1 的表达水平具有重要的临床意义.以PD-1/PD-L1 小分子抑制剂的联苯甲基芳基醚核心结构为靶向基团,引入金属离子螯合剂NOTA对其结构进行修饰,合成前体NOTA-LP.利用正电子核素68 Ga和18F分别对其进行放射性标记,获得分子探针[68 Ga]NOTA-LP和[18 F]AlF-NOTA-LP,放射化学纯度均高于95%,放射化学产率分别为 39.3%±4.8%和 21.9%±8.6%,脂水分配系数分别为 1.53±0.04和2.04±0.13.在PBS和小鼠血清中孵育 2h后,探针的放射化学纯度均大于 95%,表明其稳定性良好.细胞摄取实验证实了探针[68 Ga]NOTA-LP和[18 F]AlF-NOTA-LP可以在细胞水平上对PD-L1表达水平进行检测.
Abstract
Programmed cell death protein-1(PD-1)and its ligand 1(PD-L1)are key targets of immu-notherapy,and expression levels of PD-1 or PD-L1 are closely related to patients'response to immuno-therapy.Therefore,accurate detection of PD-1/PD-L1 expression level is of great clinical significance.It is essential to accurately select patients who can benefit from anti-PD-1/PD-L1 immunotherapy.In this study,based on the core structure of biphenyl methyl aryl ether as the core structure of PD-1/PD-L1 small molecule inhibitor,compound NOTA-LP was modified with metal ion chelating agent NO-TA.The precursor NOTA-LP was radiolabeled with 68 Ga and 18 F to obtain molecular probes[68 Ga]NOTA-LP and[18 F]AlF-NOTA-LP with the radiochemical purity of>95%.The radiochemical yield of[68 Ga]NOTA-LP and[18 F]AlF-NOTA-LP was 39.3±4.8%and 21.9±8.6%,respec-tively.The lipid-water partition coefficient of[68 Ga]NOTA-LP and[18 F]AlF-NOTA-LP was deter-mined to be1.53±0.04 and2.04±0.13,respectively.Stability of both probes was tested by incuba-ting the probes with PBS and mouse serum for 2 h,and the radiochemical purity of both probes was higher than 95%,indicating they are stable.The cell uptake assay confirmed that both probes could detect the expression level of PD-L1 at the cellular level.
关键词
程序性死亡配体-1/正电子发射计算机断层显像/小分子探针/合成/表征Key words
PD-L1/positron emission tomography/small-molecule probe/synthesis/characterization引用本文复制引用
基金项目
无锡市科技发展基金资助项目(Y20212013)
出版年
2024
NETL
NSTL
万方数据