"One Method to Label Them All": A Single Fully Automated Protocol for GMP-Compliant 68Ga Radiolabeling of PSMA-11, Transposable to PSMA-I&T and PSMA-617.

Abstract

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. 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. 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. [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. 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.