Wang Ivan E, Morrissette Luke J, Wong Ka Kit, Brooks Allen F, Dakanali Marianna, Scott Peter J H
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Radiology, University of Michigan, 2276 Medical Science 1, 1301 Catherine St., Ann Arbor, MI, 48109-5610, USA.
EJNMMI Radiopharm Chem. 2024 Dec 18;9(1):87. doi: 10.1186/s41181-024-00317-4.
Approval of Locametz and Illuccix kits for the manufacture of [Ga]Ga-PSMA-11 (gallium Ga68 gozetotide), a PET imaging agent for prostate cancer, as well as the corresponding therapeutic ([Lu]Lu-PSMA-617 Pluvicto), has led to a rapid increase in demand for [Ga]Ga-PSMA-11 PET imaging. Radiopharmaceutical manufacturers, using Ge/Ga generators, may decide to adopt Locametz and/or Illuccix kits, which requires a comparison to select the most suitable kit for day-to-day use. The objective of this article is to compare both kits and provide guidance for selecting one for routine use, as well as evaluate labeling consistency of both kits during routine production. Additionally, we report our experience during 1.5 years of daily [Ga]Ga-PSMA-11 production at our facility using both kits.
Locametz (n = 181) and Illuccix (n = 256) kits were prepared using non-silicone coated and silicone-coated needles with Ga activities ranging from 0.53 to 3.16 GBq, with a failure rate of 1 in 128 runs for both kits. With Locametz, a 3.7 GBq generator and 10-min incubation at room temperature gave doses that passed quality control (QC) testing. Use of non-silicone coated needles in the process led to solution discoloration, and QC failure. Additionally, lack of vial inversion led to inconsistent labeling, which improved with subsequent vial agitation. For Illuccix, addition of the acetate buffer to the precursor vial prior to adding the [Ga]GaCl simplifies the workflow. The maximum tolerated activity was 1.85 GBq. Lack of vial inversion led to failures, which were rectified by agitating the vial to properly incorporate the acetate solution with the generator eluate.
Both kits benefited from using a syringe pump to elute the Ge/Ga generator, vial agitation, and longer length/smaller bore silicone coated needles. Both kits have similar workflows, comparable QC outcomes, and result in equivalent clinical images. Thus, the decision between kits will ultimately be determined by production preferences. Since radiopharmacies have an established "kit-based" workflow, Locametz kits with higher allowed activities and longer shelf-life may offer benefits. Conversely, more traditional PET manufacturing facilities might benefit from using Illuccix kits due to compatibility with cyclotron-produced [Ga]GaCl allowing for kit batching. Ultimately, the commercial availability of 2 approved kits for production of [Ga]Ga-PSMA-11 PET has facilitated ready access to this important new imaging agent.
Locametz和Illuccix试剂盒被批准用于生产[Ga]Ga-PSMA-11（镓Ga68戈舍瑞林），一种用于前列腺癌的正电子发射断层扫描（PET）显像剂，以及相应的治疗药物（[Lu]Lu-PSMA-617 Pluvicto），这导致对[Ga]Ga-PSMA-11 PET显像的需求迅速增加。使用锗/镓发生器的放射性药物制造商可能会决定采用Locametz和/或Illuccix试剂盒，这需要进行比较以选择最适合日常使用的试剂盒。本文的目的是比较这两种试剂盒，为日常使用选择一种提供指导，并评估两种试剂盒在常规生产过程中的标记一致性。此外，我们报告了在我们的设施中使用这两种试剂盒进行1.5年日常[Ga]Ga-PSMA-11生产的经验。
Locametz（n = 181）和Illuccix（n = 256）试剂盒使用无硅胶涂层和硅胶涂层的针头制备，镓活度范围为0.53至3.16 GBq，两种试剂盒的故障率均为128次运行中有1次失败。对于Locametz，使用3.7 GBq的发生器并在室温下孵育10分钟可得到通过质量控制（QC）测试的剂量。在此过程中使用无硅胶涂层的针头会导致溶液变色和QC失败。此外，未进行小瓶翻转会导致标记不一致，随后通过小瓶振荡可得到改善。对于Illuccix，在加入[Ga]GaCl之前向前体小瓶中加入醋酸盐缓冲液简化了工作流程。最大耐受活度为1.85 GBq。未进行小瓶翻转会导致失败，通过振荡小瓶使醋酸盐溶液与发生器洗脱液充分混合可纠正此问题。
两种试剂盒都受益于使用注射泵洗脱锗/镓发生器、小瓶振荡以及更长长度/更小内径的硅胶涂层针头。两种试剂盒具有相似的工作流程、可比的QC结果，并能产生等效的临床图像。因此，试剂盒之间的选择最终将由生产偏好决定。由于放射性药房已建立“基于试剂盒”的工作流程，具有更高允许活度和更长保质期的Locametz试剂盒可能更具优势。相反，更传统的PET生产设施可能会受益于使用Illuccix试剂盒，因为它与回旋加速器生产的[Ga]GaCl兼容，允许进行试剂盒批量生产。最终，两种获批用于生产[Ga]Ga-PSMA-11 PET的试剂盒的商业可用性促进了对这种重要新显像剂的便捷获取。
