国产无载体镥［<superscript>177</superscript>Lu］的制备及标记 DOTA⁃TOC 在神经内分泌 肿瘤中的初步临床应用探讨.

Objective：To describe the preparation process of domestic carrier ⁃free lutetium［177Lu］and the method for labeling of 177Lu with 1, 4, 7, 10⁃tetraazacyclododecane⁃1u⁃, 4, 7, 10⁃tetraacetic acid conjugated Tyr3⁃octreotide（DOTA⁃TOC), and to explore the safety and efficacy of the preliminary clinical application of domestically produced 177Lu⁃DOTA⁃TOC. Methods：Domestic carrier⁃free lutetium［177Lu］was prepared by multistage sequential isolation and purification, and fully automated modular labeling was used to synthesize 177Lu ⁃DOTA ⁃TOC. The data of 4 patients with neuroendocrine neoplasms（NEN) in Naning Hospital Affiliated to Nanjing Medical University who only received domestic carrier⁃free lutetium［177Lu］labeled DOTA⁃TOC peptide receptor radionuclide therapy (PRRT) were retrospectively analyzed. Results：The domestic carrier⁃free lutetium［177Lu］had good quality control, with copper（Cu) <0.01, zinc（Zn) <0.01, iron（Fe) <0.01, lead（Pb) <0.15, and thulium（Yb) undetectable, radiochemical purity >99%, and bacterial endotoxin <2 EU/mL. The yield of domestic automated labeling of 177Lu⁃DOTA⁃TOC was（98.85±0.97) %, and the specific activity of the product was（80.96 ± 7.47) GBq/μmol. Sterility and endotoxin tests of the labeled product met the specified standards, and the ethanol content in the labeled product was 0, with a radiochemical purity greater than 99%. Among the 4 patients who received only domestic 177Lu⁃DOTA⁃TOC only, 1 patient showed almost complete disappearance of the primary and metastatic lesions after only one treatment, while another patient experienced grade 3 bone marrow toxicity one month after treatment, which recovered to normal after three months. None of the patients showed renal toxicity. Conclusion; Domestic carrier⁃free lutetium［177Lu］labeled DOTA⁃TOC meets quality control standards, has a high yield, good safety, and tolerability, and has good therapeutic efficacy for patients with inoperable NEN. The domestication and large⁃scale production of carrier⁃free lutetium［177Lu］will promote the integrated development of nuclear medicine diagnosis and treatment in China. [ABSTRACT FROM AUTHOR]

目的：阐述国产无载体镥［177Lu］制备工艺及177Lu标记1, 4, 7, 10⁃四氮杂环十二烷⁃1, 4, 7, 10⁃四乙酸⁃酪氨酸3⁃奥曲 肽（1, 4, 7, 10⁃tetraazacyclododecane⁃1, 4, 7, 10⁃tetraacetic acid conjugated Tyr3⁃octreotide, DOTA⁃TOC）的方法, 探讨国产177Lu⁃DO⁃ TA⁃TOC初步临床应用的安全性及有效性. 方法：采用多级连续分离纯化制备国产无载体镥［177Lu］, 全自动化模块标记合成 177Lu⁃DOTA⁃TOC, 回顾分析南京医科大学附属南京医院4例仅接受了国产无载体镥［177Lu］标记DOTA⁃TOC的肽受体放射性核 素靶向治疗（peptide receptor radionuclide therapy, PRRT）神经内分泌肿瘤（neuroendocrine neoplasm, NEN）患者资料. 结果：国 产无载体镥［177Lu］质控良好, 铜<0.01, 锌<0.01, 铁<0.01, 铅<0.15, 镱未检出, 放化纯＞99%, 细菌内毒素<2 EU/mL. 国产177Lu⁃ DOTA⁃TOC自动化标记产率为（98.85±0.97）%, 产品比活度为（80.96±7.47）GBq/μmol, 无菌和内毒素检测均符合规定标准, 标记 产物中乙醇含量为0, 放化纯大于99%. 仅接受国产177Lu⁃DOTA⁃TOC治疗的4例患者中, 1例仅1次治疗后原发灶及转移灶几 乎完全消失, 1例治疗后1个月出现3级骨髓毒性, 治疗后3个月恢复至正常, 所有患者均未出现肾毒性. 结论：国产无载体镥 ［177Lu］标记DOTA⁃TOC质控合格, 产率高, 安全、耐受性好, 对于无法手术切除的NEN患者具有较好疗效. 无载体镥［177Lu］的 国产化和批量化生产将推动我国核医学诊疗一体化的发展. [ABSTRACT FROM AUTHOR]