Pretze Marc, Kunkel Falk, Runge Roswitha, Freudenberg Robert, Braune Anja, Hartmann Holger, Schwarz Uwe, Brogsitter Claudia, Kotzerke Jörg
Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany.
Molecular Imaging and Radiochemistry, Department of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Pharmaceuticals (Basel). 2021 Jul 6;14(7):652. doi: 10.3390/ph14070652.
The application of Ac (half-life T = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to Y, Lu or Re while maintaining the therapeutic outcome. Additionally, the range of alpha particles of Ac and its daughter nuclides in tissue is much lower (47-85 μm for alpha energies E = 5.8-8.4 MeV), which results in a very precise dose deposition within the tumor. DOTA-conjugated commercially available peptides used for endoradiotherapy, which can readily be labeled with Lu or Y, can also accommodate Ac. The benefits are lower doses in normal tissue for the patient, dose reduction of the employees and environment and less shielding material. The low availability of Ac activity is preventing its application in clinical practice. Overcoming this barrier would open a broad field of Ac therapy. Independent which production pathway of Ac proves the most feasible, the use of automated synthesis and feasible and reproducible patient doses are needed. The Modular-Lab EAZY is one example of a GMP-compliant system, and the cassettes used for synthesis are small. Therefore, also the waste after the synthesis can be minimized. In this work, two different automated setups with different purification systems are presented. In its final configuration, three masterbatches were performed on the ML EAZY for DOTA-TATE and PSMA-I&T, respectively, fulfilling all quality criteria with final radiochemical yields of 80-90% for the Ac-labeled peptides.
与钇、镥或铼相比，锕（半衰期T = 9.92天）的应用可将用于肽受体放射性核素治疗的活度显著降低1000倍，同时保持治疗效果。此外，锕及其子核素在组织中的α粒子射程要低得多（α能量E = 5.8 - 8.4 MeV时为47 - 85μm），这使得肿瘤内的剂量沉积非常精确。用于内放射治疗的与DOTA偶联的市售肽，可轻松用镥或钇标记，也可容纳锕。其好处是患者正常组织中的剂量更低、员工和环境的剂量降低以及屏蔽材料减少。锕活度的低可用性阻碍了其在临床实践中的应用。克服这一障碍将开启广阔的锕治疗领域。无论哪种锕的生产途径被证明最可行，都需要使用自动化合成以及可行且可重复的患者剂量。模块化实验室EAZY就是一个符合GMP标准的系统示例，用于合成的盒体很小。因此，合成后的废物也可减至最少。在这项工作中，展示了两种配备不同纯化系统的不同自动化装置。在其最终配置中，分别在ML EAZY上对DOTA - TATE和PSMA - I&T进行了三批母液制备，所有质量标准均得到满足，锕标记肽的最终放射化学产率为80 - 90%。
