Antonella Iudicello1,2, Filippo Genovese3, Valentina Di Iorio4, Gianfranco Cicoria5, Stefano Boschi6. 1. Pharmaceutical Department, Azienda USL of Modena, Largo del Pozzo, 71, 41121, Modena, Italy. a.iudicello@ausl.mo.it. 2. Oncology and Hematology Department, Nuclear Medicine Unit, Azienda Ospedaliero-Universitaria of Modena, Largo del Pozzo, 71, 41121, Modena, Italy. a.iudicello@ausl.mo.it. 3. Centro Interdipartimentale Grandi Strumenti, University of Modena and Reggio Emilia, Via Campi 213/A, 41125, Modena, Italy. 4. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS IRST, Via Piero Maroncelli, 40, 47014, Meldola, FC, Italy. 5. Medical Physics Department, Azienda Ospedaliero-Universitaria of Modena, Largo del Pozzo, 71, 41121, Modena, Italy. 6. Department for Life Quality Studies, University of Bologna, Corso D'Augusto, 237, Rimini, 47921, Italy.
Abstract
BACKGROUND: The stability of precursors and reagents is of utmost importance for developing a robust radiolabelling method that provides high and constant radiochemical yield and radiochemical purity. While performing the QC of the [68Ga]Ga-PSMA-11 injectable solutions according to Ph. Eur. Monograph that has recently been published, a trend to the instability of the standard PSMA-11, the same used as a precursor for [68Ga]Ga-PSMA-11 radiosynthesis, has been observed. This instability led to the formation of a side product in a time-dependent manner. The formation of this compound, besides making the implementation of the Ph. Eur. analytical method more difficult, negatively influenced the radiochemical yield and the radiochemical purity by increasing gallium-68 in colloidal and ionic forms. RESULTS: The nature of the side product was investigated by adding chelators, such as EDTA, to PSMA-11 solutions and using the combination of UHPLC-HRMS. The results led to the definition of the side product structure, as natFe-PSMA-11, from the combination of the high-affinity chelator HBED-CC, present in the molecule of PSMA-11, and environmental Fe (III). CONCLUSIONS: Strategies to reduce the risk of low radiolabeling yields and to increase the stability of the PSMA-11 in an aqueous solution were also discussed.
BACKGROUND: The stability of precursors and reagents is of utmost importance for developing a robust radiolabelling method that provides high and constant radiochemical yield and radiochemical purity. While performing the QC of the [68Ga]Ga-PSMA-11 injectable solutions according to Ph. Eur. Monograph that has recently been published, a trend to the instability of the standard PSMA-11, the same used as a precursor for [68Ga]Ga-PSMA-11 radiosynthesis, has been observed. This instability led to the formation of a side product in a time-dependent manner. The formation of this compound, besides making the implementation of the Ph. Eur. analytical method more difficult, negatively influenced the radiochemical yield and the radiochemical purity by increasing gallium-68 in colloidal and ionic forms. RESULTS: The nature of the side product was investigated by adding chelators, such as EDTA, to PSMA-11 solutions and using the combination of UHPLC-HRMS. The results led to the definition of the side product structure, as natFe-PSMA-11, from the combination of the high-affinity chelator HBED-CC, present in the molecule of PSMA-11, and environmental Fe (III). CONCLUSIONS: Strategies to reduce the risk of low radiolabeling yields and to increase the stability of the PSMA-11 in an aqueous solution were also discussed.
Authors: Wolfgang P Fendler; Matthias Eiber; Mohsen Beheshti; Jamshed Bomanji; Francesco Ceci; Steven Cho; Frederik Giesel; Uwe Haberkorn; Thomas A Hope; Klaus Kopka; Bernd J Krause; Felix M Mottaghy; Heiko Schöder; John Sunderland; Simon Wan; Hans-Jürgen Wester; Stefano Fanti; Ken Herrmann Journal: Eur J Nucl Med Mol Imaging Date: 2017-06 Impact factor: 9.236
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Authors: Nic Gillings; Sergio Todde; Martin Behe; Clemens Decristoforo; Philip Elsinga; Valentina Ferrari; Olaug Hjelstuen; Petra Kolenc Peitl; Jacek Koziorowski; Peter Laverman; Thomas L Mindt; Meltem Ocak; Marianne Patt Journal: EJNMMI Radiopharm Chem Date: 2020-02-12