Hunt William W, Long Mathew, Kamil Usama, Kellapatha Sunil, Noonan Wayne, Roselt Peter D, Emmerson Brittany, Hofman Michael S, Haskali Mohammad B
Department of Radiopharmaceutical Sciences, Cancer Imaging, The Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
Nat Protoc. 2025 May 27. doi: 10.1038/s41596-025-01176-2.
Theranostics utilizes tandem targeted diagnostic and therapeutic agents that are molecularly analogous. In a theranostic approach, the diagnostic agent is a tracer typically radiolabeled with a positron emission tomography radionuclide such as fluorine-18 or gallium-68. Utilizing the selectivity of the tracer, the therapeutic agent is subsequently radiolabeled with an ablative radionuclide such as the β emitting lanthanide lutetium-177 (Lu). Lu is typically incorporated into theranostics using the chelators 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) and 2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)pentanedioic acid (DOTAGA) that are used to prepare the Lu-radiopharmaceutical [Lu]Lu-DOTA-TATE, [Lu]Lu-PSMA-617 and [Lu]Lu-PSMA-I&T. Here we describe the scalable and validated production for these Lu-radiopharmaceuticals and further include the necessary quality control protocols. The procedures can be generalized and support both carrier added and noncarrier added Lu sources for use in a clinical setting. With robust procedures that accommodate Lu activity levels from 5 to 100 GBq, the procedures ensure stability for up to 8 h postproduction and achieve an average activity yield of 98%. As proven in over 1,000 patient cycles, this methodology is adaptable to both centralized production facilities and regional centers, enabling versatile application across small and large-scale production settings.
治疗诊断学利用分子结构类似的串联靶向诊断和治疗剂。在治疗诊断方法中，诊断剂是一种示踪剂，通常用正电子发射断层扫描放射性核素如氟 - 18或镓 - 68进行放射性标记。利用示踪剂的选择性，治疗剂随后用消融性放射性核素如发射β射线的镧系元素镥 - 177（Lu）进行放射性标记。Lu通常使用螯合剂2,2',2'',2'''-(1,4,7,10 - 四氮杂环十二烷 - 1,4,7,10 - 四基)四乙酸（DOTA）和2-(4,7,10 - 三(羧甲基)-1,4,7,10 - 四氮杂环十二烷 - 1 - 基)戊二酸（DOTAGA）掺入治疗诊断剂中，这些螯合剂用于制备Lu放射性药物[Lu]Lu - DOTA - TATE、[Lu]Lu - PSMA - 617和[Lu]Lu - PSMA - I&T。在此，我们描述了这些Lu放射性药物的可扩展且经过验证的生产过程，并进一步包括必要的质量控制方案。这些程序可以推广，并支持在临床环境中使用添加载体和不添加载体的Lu源。通过适用于5至100 GBq的Lu活度水平的稳健程序，这些程序可确保生产后长达8小时的稳定性，并实现98%的平均活度产率。正如在超过1000个患者周期中所证明的那样，这种方法适用于集中生产设施和区域中心，能够在小规模和大规模生产环境中广泛应用。
