Klinik für Nuklearmedizin, Universitätsklinikum Essen (AöR), Hufelandstraße 55, D-45147 Essen, Germany.
SOFIE, iTheranostics, 21000 Atlantic Boulevard, Dulles, VA 20166, USA.
Nucl Med Biol. 2022 Jul-Aug;110-111:37-44. doi: 10.1016/j.nucmedbio.2022.04.010. Epub 2022 Apr 30.
With respect to the broad application of FAPI-46 in therapy and diagnostics, there is a need for an efficient as well as convenient way for routine production and quality control of the theranostic pair [Y]Y/[Ga]Ga-FAPI-46, since no monograph is currently available for radiolabelled FAPI derivatives. The aim of the current work is to create a GMP compliant theranostic set up for the production and quality control of the diagnostic [Ga]Ga-FAPI-46 as well as the therapeutic drug [90 Y]Y-FAPI-46, which can be the basis for future monographic standards.
Sterile [Y]yttrium chloride solution and a pharmaceutical grade Ge/Ga generator were applied for the labelling of FAPI-46 using the cassette based synthesis module Trasis EASYONE. All chemicals were GMP-grade and excipients were with marketing authorisation. The quality control included test procedures according to Ph. Eur.
Fully automated synthesis of the theranostic pair [Y]Y/[Ga]Ga-FAPI-46 was achieved on the Trasis EasyOne synthesizer with a radiochemical yield of 88 ± 7% and 56 ± 5% with a radiochemical purity of >99%. Stability experiments showed a durability for [Ga]Ga-FAPI-46 within 4 h and for [Y]Y-FAPI-46 within 24 h. All obtained specifications and validations were compliant with the European Pharmacopoeia and regulatory guidelines. Both products were successfully applied in cancer patients.
In the present work, efficient and robust procedures for the automated production and quality control of the theranostic pair [Ga]/[Y]FAPI 46 were developed and validated using the same synthetic platform. The described methods were evaluated in accordance with existing guidelines and toxicological limits, which can be a valuable basis for future monographic standards.
由于目前尚无放射性标记 FAPI 衍生物的专论，因此需要一种高效、便捷的方法来常规生产和质量控制治疗和诊断用的 FAPI-46 乏试剂，以便广泛应用 FAPI-46。本研究旨在建立一种符合 GMP 标准的诊断用 [Ga]Ga-FAPI-46 和治疗药物 [90Y]Y-FAPI-46 的生产和质量控制的治疗诊断试剂盒，为未来的专论标准提供基础。
使用基于盒式的 Trasis EASYONE 合成模块，用无菌 [Y]钇氯化物溶液和医药级锗/镓发生器对 FAPI-46 进行标记。所有化学物质均为 GMP 级，赋形剂均具有上市许可。质量控制包括按照欧洲药典进行的测试程序。
在 Trasis EasyOne 合成仪上，通过全自动合成方法，成功制备了治疗诊断试剂盒[Y]Y/[Ga]Ga-FAPI-46，其放射性化学产率分别为 88±7%和 56±5%，放射性化学纯度>99%。稳定性实验表明，[Ga]Ga-FAPI-46 在 4 小时内稳定，[Y]Y-FAPI-46 在 24 小时内稳定。所有获得的规格和验证均符合欧洲药典和监管指南的要求。两种产品均成功应用于癌症患者。
本研究使用相同的合成平台，开发并验证了用于治疗诊断试剂盒[Ga]/[Y]FAPI 46 的自动化生产和质量控制的高效、稳健的程序。所描述的方法是根据现有指南和毒理学限度进行评估的，这可为未来的专论标准提供有价值的基础。
