Preparation and labeling of domestic carrier ⁃ free lutetium[177Lu]and preliminary clinical application discussion of DOTA⁃TOC in neuroendocrine tumors
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    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(自然科学版英文版),2024,(2):235-241.

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  • Received:October 29,2023
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  • Online: February 05,2024
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