Iudicello Antonella, Genovese Filippo, Di Iorio Valentina, Cicoria Gianfranco, Boschi Stefano
Pharmaceutical Department, Azienda USL of Modena, Largo del Pozzo, 71, 41121, Modena, Italy.
Oncology and Hematology Department, Nuclear Medicine Unit, Azienda Ospedaliero-Universitaria of Modena, Largo del Pozzo, 71, 41121, Modena, Italy.
EJNMMI Radiopharm Chem. 2021 Mar 24;6(1):14. doi: 10.1186/s41181-021-00122-3.
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 [Ga]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 [Ga]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.
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 Fe-PSMA-11, from the combination of the high-affinity chelator HBED-CC, present in the molecule of PSMA-11, and environmental Fe (III).
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.
前体和试剂的稳定性对于开发一种稳健的放射性标记方法至关重要，该方法可提供高且恒定的放射化学产率和放射化学纯度。在根据最近发布的欧洲药典专论对[镓]镓 - PSMA - 11注射溶液进行质量控制时，观察到标准PSMA - 11（用作[镓]镓 - PSMA - 11放射性合成前体）存在不稳定趋势。这种不稳定性导致以时间依赖的方式形成一种副产物。该化合物的形成，除了使欧洲药典分析方法的实施更加困难外，还通过增加胶体和离子形式的镓 - 68对放射化学产率和放射化学纯度产生负面影响。
通过向PSMA - 11溶液中添加螯合剂（如EDTA）并使用UHPLC - HRMS联用技术研究了副产物的性质。结果确定了副产物结构为Fe - PSMA - 11，它是由PSMA - 11分子中存在的高亲和力螯合剂HBED - CC与环境中的铁（III）结合而成。
还讨论了降低低放射性标记产率风险以及提高PSMA - 11在水溶液中稳定性的策略。
