国产无载体镥[177Lu]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
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R736

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江苏省重点研发专项基金(BE2017612);南京市医学科技发展重点项目(ZKX17027);南京市医疗卫生国际联合研发项目(201911042);绵阳市中心医院核医学实验室开放课题(2021HYX009)


Preparation and labeling of domestic carrier ⁃ free lutetium[177Lu]and preliminary clinical application discussion of DOTA⁃TOC in neuroendocrine tumors
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    摘要:

    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:

    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.

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姚晓晨,张朋俊,陈正国,杨宇川,田瑞,俞飞,王峰.国产无载体镥[177Lu]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[J].南京医科大学学报(自然科学版),2024,(2):235-241

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  • 收稿日期:2023-10-29
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  • 在线发布日期: 2024-02-05
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