^(68)Ga标记GIPR靶向探针的合成及其初步生物学评价

Synthesis and Preliminary Biological Evaluation of ^(68)Ga-labeled GIPR Targeting Probe

葡萄糖依赖性胰岛素释放肽受体(GIPR)是神经内分泌肿瘤(NETs)的重要靶标之一。本研究构建了新型的GIPR靶向探针^(68)Ga-DOTA-GIP(1-30)-F-02,通过模块进行自动化标记,考察该方法制备的^(68)Ga-DOTA-GIP(1-30)-F-02的标记率、放化纯度及体外稳定性。用正常ICR小鼠进行生物分布研究,并建立PC12-hGIP细胞荷瘤鼠模型进行Micro-PET/CT显像研究。结果表明,^(68)Ga-DOTA-GIP(1-30)-F-02自动化标记简易方便,标记率为(65.32±1.57)%,放化纯度>99%,体外稳定性良好。生物分布显示,^(68)Ga-DOTAGIP(1-30)-F-02在正常组织摄取较低,主要通过肾脏代谢,Micro-PET/CT显像该探针在给药后60 min肿瘤部位放射性摄取值可达(6.51±1.03)%ID/g,具有较好的肿瘤显像效果,初步表明,该探针具有用于神经内分泌肿瘤靶向显像的可行性和特异性。

Glucose-dependent insulinotropic polypeptide receptor(GIPR)is one of the important targets of neuroendocrine tumors(NETs).In this study,a novel GIPR targeting probe^(68)Ga-DOTAGIP(1-30)-F-02 was constructed through the module for automatic labeling.The labeling yield,radiochemical purity,and in vitro stability of this probe were investigated.The biodistribution in normal ICR mice and Micro-PET/CT imaging of PC12-hGIP tumor-bearing mouse models were studied.The results showed that the automatic method for^(68)Ga-DOTA-GIP(1-30)-F-02 preparation was simple and convenient with a good radiochemical yield of(65.32±1.57)%,high radiochemical purity(>99%),and good in vitro stability.The results of biodistribution showed low uptakes of^(68)Ga-DOTA-GIP(1-30)-F-02 in normal tissues,mainly excreted through the renal urinary system.Micro-PET/CT imaging showed the uptake at the tumor site reached(6.51±1.03)%ID/g at 60 min post-injection which indicates good tumor imaging potentiality.The feasibility and specificity of the probe for GIPR-targeted imaging of neuroendocrine tumors were preliminarily demonstrated.