Development of [225ac]ac-psma-i&t for targeted alpha therapy according to gmp guidelines for treatment of mcrpc

Eline L. Hooijman, Yozlem Chalashkan, Sui Wai Ling, Figen F. Kahyargil, Marcel Segbers, Frank Bruchertseifer, Alfred Morgenstern, Yann Seimbille, Stijn L.W. Koolen, Tessa Brabander, Erik de Blois*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Recently, promising results of the antitumor effects were observed in patients with metastatic castration-resistant prostate cancer treated with177Lu-labeled PSMA-ligands. Radionu-clide therapy efficacy may even be improved by using the alpha emitter Ac-225. Higher efficacy is claimed due to high linear energy transfer specifically towards PSMA positive cells, causing more double-strand breaks. This study aims to manufacture [225Ac]Ac-PSMA-I&T according to good manufacturing practice guidelines for the translation of [225Ac]Ac-PSMA-I&T into a clinical phase 1 dose escalation study. Quencher addition during labeling was investigated. Quality control of [225Ac]Ac-PSMA-I&T was based on measurement of Fr-221 (218 keV), in equilibrium with Ac-225 in approximately six half-lives of Fr-221 (T12 = 4.8 min). Radio-(i)TLC methods were utilized for identification of the different radiochemical forms, gamma counter for concentration determination, and HPGe-detector for the detection of the radiochemical yield. Radiochemical purity was determined by HPLC. The final patient dose was prepared and diluted with an optimized concentration of quenchers as during labeling, with an activity of 8–12 MBq (±5%), pH > 5.5, 100 ± 20 µg/dose, PSMA-I&T, radiochemical yield >95%, radiochemical purity >90% (up to 3 h), endotoxin levels of <5 EU/mL, osmolarity of 2100 mOsmol, and is produced according to current guidelines. The start of the phase I dose escalation study is planned in the near future.

Original languageEnglish
Article number715
JournalPharmaceutics
Volume13
Issue number5
DOIs
Publication statusPublished - 13 May 2021

Bibliographical note

Funding Information:
Acknowledgments: The authors would like to thank the support given by the colleagues of the Department of Radiology and Nuclear Medicine and the Department of Pharmacy of the Erasmus Medical Center for enabling this research. In particular, we want to thank Simone Morelis, Pieter Meppelink, Emar Thomasa, and Heleen Voorwinden for their support during implementation. For support regarding radioprotection advice and health physics, we want to thank M.W. Konijnenberg.

Funding Information:
Funding: This research was funded by the KWF, grant number 1190.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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