PDF(Pubmed)
Abstract：
BACKGROUND: 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 68Ga for PET imaging. The 68Ga radiolabeling step benefits from process automation, making it more robust and reducing radiation exposure.
OBJECTIVE: To design a single automated radiolabeling protocol for the GMP-compliant preparation of [68Ga]Ga-PSMA-11, transposable to the production of [68Ga]Ga-PSMA-617 and [68Ga]Ga-PSMA-I&T.
METHODS: A GAIA® synthesis module and a GALLIAD® generator were used. Radio-TLC and radio-HPLC methods were validated for radiochemical purity (RCP) determination. Three [68Ga]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.
RESULTS: [68Ga]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.
CONCLUSIONS: A single automated radiolabeling method on the GAIA® module was developed and implemented for 68Ga radiolabeling of 3 PSMA ligands, with slight adjustments for each molecule.
OBJECTIVE: To design a single automated radiolabeling protocol for the GMP-compliant preparation of [68Ga]Ga-PSMA-11, transposable to the production of [68Ga]Ga-PSMA-617 and [68Ga]Ga-PSMA-I&T.
METHODS: A GAIA® synthesis module and a GALLIAD® generator were used. Radio-TLC and radio-HPLC methods were validated for radiochemical purity (RCP) determination. Three [68Ga]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.
RESULTS: [68Ga]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.
CONCLUSIONS: A single automated radiolabeling method on the GAIA® module was developed and implemented for 68Ga radiolabeling of 3 PSMA ligands, with slight adjustments for each molecule.
摘要：
背景：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标。因此,开发了各种PSMA配体。这些分子中的一些被可以容纳放射性金属的螯合剂官能化，如68Ga用于PET成像。68Ga放射性标记步骤受益于过程自动化，使其更坚固，减少辐射暴露。
目的：为符合GMP的[68Ga]Ga-PSMA-11的制备设计一种单一的自动放射性标记方案，可转座至[68Ga]Ga-PSMA-617和[68Ga]Ga-PSMA-I&T的生产。
方法:使用GAIA®合成模块和GALLIAD®发生器。验证了放射性TLC和放射性HPLC方法的放射化学纯度（RCP）测定。生产了三个[68Ga]Ga-PSMA-11验证批次，并对外观和pH进行了彻底测试。放射性核素鉴定和纯度，RCP,稳定性,残留溶剂和无菌。对试剂和一次性用品进行了最小的修饰，以最佳地应用于其他PSMA配体。
结果:用于临床应用的[68Ga]Ga-PSMA-11在27分钟内产生。3个验证批次符合欧洲药典所预期的允许常规生产的质量标准。为了最佳地转座至PSMA-617,改变固相萃取柱以改善放射性标记产物的纯化。对于PSMA-I&T的应用，最初使用的缓冲溶液被HEPES2.7M替代,以获得良好的放射化学产率.在最终产品中检查残留HEPES含量,并且低于Ph。欧尔.阈值。
结论：开发并实施了GAIA®模块上的单一自动放射性标记方法，用于3个PSMA配体的68Ga放射性标记，对每个分子进行轻微调整。
目的：为符合GMP的[68Ga]Ga-PSMA-11的制备设计一种单一的自动放射性标记方案，可转座至[68Ga]Ga-PSMA-617和[68Ga]Ga-PSMA-I&T的生产。
方法:使用GAIA®合成模块和GALLIAD®发生器。验证了放射性TLC和放射性HPLC方法的放射化学纯度（RCP）测定。生产了三个[68Ga]Ga-PSMA-11验证批次，并对外观和pH进行了彻底测试。放射性核素鉴定和纯度，RCP,稳定性,残留溶剂和无菌。对试剂和一次性用品进行了最小的修饰，以最佳地应用于其他PSMA配体。
结果:用于临床应用的[68Ga]Ga-PSMA-11在27分钟内产生。3个验证批次符合欧洲药典所预期的允许常规生产的质量标准。为了最佳地转座至PSMA-617,改变固相萃取柱以改善放射性标记产物的纯化。对于PSMA-I&T的应用，最初使用的缓冲溶液被HEPES2.7M替代,以获得良好的放射化学产率.在最终产品中检查残留HEPES含量,并且低于Ph。欧尔.阈值。
结论：开发并实施了GAIA®模块上的单一自动放射性标记方法，用于3个PSMA配体的68Ga放射性标记，对每个分子进行轻微调整。
