^(18)F标记胰高血糖素样肽-1受体激动剂探针的合成及在胰岛素瘤PET/CT诊断中的初步评价  

Synthesis of^(18)F-labeled glucagon-like peptide-1 receptor agonist targeting probe and its preliminary evaluation in diagnosis of insulinoma with PET/CT

作　　者：谢运飞 刘楠 刘兆辉 何丽萌 马欢 刘浩[1] 王浩 高海燕[1] 张卫玮 张伟[1] Xie Yunfei;Liu Nan;Liu Zhaohui;He Limeng;Ma Huan;Liu Hao;Wang Hao;Gao Haiyan;Zhang Weiwei;Zhang Wei(Department of Nuclear Medicine,Sichuan Academy of Medical Sciences-Sichuan Provincial People′s Hospital(Affiliated Hospital of University of Electronic Science and Technology),Chengdu 610072,China)

机构地区：[1]四川省医学科学院·四川省人民医院(电子科技大学附属医院)核医学科,成都610072

出　　处：《中华核医学与分子影像杂志》2024年第11期673-677,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：四川省自然科学基金(2023NSFSC0635)。

摘　　要：目的探索胰高血糖素样肽-1受体激动剂^(18)F-AlF-1,4,7-三氮杂环壬烷-1,4,7-三乙酸(NOTA)-马来酰亚胺(Mal)-半胱氨酸(Cys)^(39)-exendin-4(简称^(18)F-exendin-4)的自动化合成,并验证其在胰岛素瘤PET/CT显像中的诊断效能。方法以NOTA-Mal-Cys^(39)-exendin-4为标记前体,通过Al^(18)F一步法,利用All in one多功能化学合成器进行放射性标记、纯化及制剂化得到^(18)F-exendin-4,产品经质量控制合格后,对1例临床怀疑胰岛素瘤的患者(女,55岁)行^(18)F-exendin-4 PET/CT显像。结果^(18)F-exendin-4的放射性标记耗时约40 min,计算未衰减校正的合成产率为(18.03±2.67)%(n=3),比活度>39.74 GBq/μmol,放射性浓度>390.00 MBq/ml。产品为无色透明液体,pH值6.5,放化纯>96%,细菌及内毒素指标均符合《中华人民共和国药典(2020年版)》标准。PET/CT图像分析结果示,患者胰腺体部见结节状^(18)F-exendin-4高摄取。术后病理及肿瘤细胞免疫组织化学证实符合神经内分泌肿瘤(G2)特征。结论实现自动化合成^(18)F-exendin-4,并证实其在胰岛素瘤的诊断中具有临床价值,适宜在配备医用回旋加速器的医疗机构推广使用。Objective To explore the automated synthesis of glucagon-like peptide-1 receptor agonist^(18)F-AlF-1,4,7-triazacyclononane-1,4,7-triacetic acid(NOTA)-maleimide(Mal)-cysteine(Cys)^(39)-exendin-4(^(18)F-exendin-4),and verify its diagnostic efficacy on insulinoma with PET/CT.Methods Using NOTA-Mal-Cys^(39)-exendin-4 as the labeled precursor,^(18)F-exendin-4 was obtained by constructing Al^(18)F one-step reaction sequence and using All in one multifunctional chemical synthesizer for radiolabelling,purification and preparation.After the quality control,^(18)F-exendin-4 PET/CT imaging was performed on 1 patient(female,55 years old)with clinical suspicion of insulinoma.Results Radiolabelling of^(18)F-exendin-4 took about 40 min,with the non-decay corrected radiochemical yield of(18.03±2.67)%(n=3),the molar activity>39.74 GBq/μmol,and the radioactivity concentration>390.00 MBq/ml.The injection was a colorless transparent liquid with pH value of 6.5,and the radiochemical purity>96%.Results of bacteria and endotoxins testing met the standards of Pharmacopoeia of the People′s Republic of China(2020).PET/CT image analysis showed a nodular high uptake of^(18)F-exendin-4 in the pancreatic body.The pathological and immunohistochemical results were consistent with the characteristics of neuroendocrine neoplasm(G2).Conclusions The automatic radiolabelling of^(18)F-exendin-4 is successfully realized by All in one multifunctional chemical synthesizer.^(18)F-exendin-4 has been proved to be of clinical value in diagnosis of insulinoma,and is suitable for promotion in medical institutions equipped with medical cyclotrons.

关 键 词：胰岛素瘤 胰高血糖素样肽-1受体激动剂 艾塞那肽 氟放射性同位素 正电子发射断层显像术 体层摄影术 X线计算机 

分 类 号：R736.7[医药卫生—肿瘤] R730.44[医药卫生—临床医学]