Production and Quality Control of [ 177 Lu]Lu-PSMA-I&T: Development of an Investigational Medicinal Product Dossier for Clinical Trials.
In: Molecules, Jg. 27 (2022-07-01), Heft 13, S. 4143-4157
Online
academicJournal
Zugriff:
Since prostate cancer is the most commonly diagnosed malignancy in men, the theranostic approach has become very attractive since the discovery of urea-based PSMA inhibitors. Different molecules have been synthesized starting from the Glu-urea-Lys scaffold as the pharmacophore and then optimizing the linker and the chelate to improve functional characteristics. This article aimed to highlight the quality aspects, which could have an impact on clinical practice, describing the development of an Investigational Medicinal Product Dossier (IMPD) for clinical trials with [ 177 Lu]Lu-PSMA-I&T in prostate cancer and other solid tumors expressing PSMA. The results highlighted some important quality issues of the final preparation: radiolabeling of PSMA-I&T with lutetium-177 needs a considerably longer time compared with the radiolabeling of the well-known [ 177 Lu]Lu-PSMA-617. When the final product was formulated in saline, the stability of [ 177 Lu]Lu-PSMA-I&T was reduced by radiolysis, showing a decrease in radiochemical purity (<95% in 24 h). Different formulations of the final product with increasing concentrations of ascorbic acid have been tested to counteract radiolysis and extend stability. A solution of 20 mg/mL of ascorbic acid in saline prevents radiolysis and ensures stability over 30 h. [ABSTRACT FROM AUTHOR]
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Titel: |
Production and Quality Control of [ 177 Lu]Lu-PSMA-I&T: Development of an Investigational Medicinal Product Dossier for Clinical Trials.
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Autor/in / Beteiligte Person: | Di Iorio, Valentina ; Boschi, Stefano ; Cuni, Cristina ; Monti, Manuela ; Severi, Stefano ; Paganelli, Giovanni ; Masini, Carla |
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Zeitschrift: | Molecules, Jg. 27 (2022-07-01), Heft 13, S. 4143-4157 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 1420-3049 (print) |
DOI: | 10.3390/molecules27134143 |
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