Nuclear Medicine Department, Institut Régional du Cancer de Montpellier (ICM), University of Montpellier, Montpellier, France.
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, University of Montpellier, Montpellier, France.
Curr Radiopharm. 2024;17(3):285-301. doi: 10.2174/0118744710293461240219111852.
Prostate-specific membrane antigen (PSMA) is an ideal target for molecular imaging and targeted radionuclide therapy in prostate cancer. Consequently, various PSMA ligands were developed. Some of these molecules are functionalized with a chelator that can host radiometals, such as Ga for PET imaging. The Ga radiolabeling step benefits from process automation, making it more robust and reducing radiation exposure.
To design a single automated radiolabeling protocol for the GMP-compliant preparation of [Ga]Ga-PSMA-11, transposable to the production of [Ga]Ga-PSMA-617 and [Ga]Ga-PSMA-I&T.
A GAIA synthesis module and a GALLIAD generator were used. Radio-TLC and radio-HPLC methods were validated for radiochemical purity (RCP) determination. Three [Ga]Ga-PSMA-11 validation batches were produced and thoroughly tested for appearance and pH, radionuclide identity and purity, RCP, stability, residual solvent and sterility. Minimal modifications were made to the reagents and disposables for optimal application to other PSMA ligands.
[Ga]Ga-PSMA-11 for clinical application was produced in 27 min. The 3 validation batches met the quality criteria expected by the European Pharmacopoeia to allow routine production. For optimal transposition to PSMA-617, the solid phase extraction cartridge was changed to improve purification of the radiolabeled product. For application to PSMA-I&T, the buffer solution initially used was replaced by HEPES 2.7 M to achieve good radiochemical yields. Residual HEPES content was checked in the final product and was below the Ph. Eur. threshold.
A single automated radiolabeling method on the GAIA module was developed and implemented for Ga radiolabeling of 3 PSMA ligands, with slight adjustments for each molecule.
前列腺特异性膜抗原（PSMA）是前列腺癌分子成像和靶向放射性核素治疗的理想靶点。因此，开发了各种 PSMA 配体。其中一些分子用螯合剂官能化，可以容纳放射性金属，如 Ga 用于 PET 成像。Ga 放射性标记步骤得益于自动化处理，使其更稳健并减少辐射暴露。
设计一种符合 GMP 的 [Ga]Ga-PSMA-11 自动化放射性标记方案，可转移用于制备 [Ga]Ga-PSMA-617 和 [Ga]Ga-PSMA-I&T。
使用 GAIA 合成模块和 GALLIAD 发生器。放射性 TLC 和放射性 HPLC 方法经过验证，可用于测定放射化学纯度 (RCP)。制备了三个 [Ga]Ga-PSMA-11 验证批次，并对外观和 pH 值、放射性核素身份和纯度、RCP、稳定性、残留溶剂和无菌性进行了全面测试。对试剂和一次性用品进行了最小的修改，以实现最佳应用于其他 PSMA 配体。
临床应用的 [Ga]Ga-PSMA-11 可在 27 分钟内制备。3 批验证批次符合欧洲药典预期的质量标准，允许常规生产。为了最佳转移到 PSMA-617，固相萃取柱进行了更改，以改善放射性标记产物的纯化。对于 PSMA-I&T 的应用，最初使用的缓冲液溶液被 HEPES 2.7 M 取代，以实现良好的放射化学产率。最终产品中残留的 HEPES 含量已检查，低于 Ph. Eur. 阈值。
开发并实施了一种在 GAIA 模块上的单一自动化放射性标记方法，用于 3 种 PSMA 配体的 Ga 放射性标记，每个分子只需进行轻微调整。
