TY - JOUR T1 - PSMA-GCK01 - A Generator-Based <sup>99m</sup>Tc-/<sup>188</sup>Re-Theranostic Ligand for the Prostate-Specific Membrane Antigen JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.122.264944 SP - jnumed.122.264944 AU - Jens Cardinale AU - Frederik L. Giesel AU - Christina Wensky AU - Hendrik G. Rathke AU - Uwe Haberkorn AU - Clemens Kratochwil Y1 - 2023/02/01 UR - http://jnm.snmjournals.org/content/early/2023/02/09/jnumed.122.264944.abstract N2 - Introduction: Prostate-specific membrane antigen (PSMA)-theranostic has been introduced with Gallium-68 and Lutetium-177, the currently most used radionuclides. However, Rhenium-188 is a well-known generator based therapeutic nuclide completing a theranostic tandem with Technetium-99m and may offer an interesting alternative to the current state of the art. In the present work, we aimed towards the development of a PSMA-targeted 99mTc-/188Re-theranostic tandem. Methods: The ligand HYNIC-iPSMA was chosen as lead structure. Its HYNIC chelator has limitations for 188Re-labeling and was exchanged by MAS3 to obtain PSMA-GCK01, as precursor for stable 99mTc- and 188Re-labeling. [99mTc]Tc-PSMA-GCK01 was used for the in-vitro evaluation of the novel ligand and comparison with [99mTc]Tc-EDDA/HYNIC-iPSMA. Planar imaging using 99mTc-PSMA-GCK01 and organ biodistribution with 188Re-PSMA-GCK01 were done using LNCaP-tumor bearing mice, respectively. Finally, the theranostic tandem was applied for imaging and therapy in three prostate cancer patients in compassionate care. Results: An efficient radiolabeling of PSMA-GCK01 with both radionuclides was demonstrated. Cell-based assays with 99mTc-PSMA-GCK01 vs 99mTc-EDDA/HYNIC-iPSMA revealed comparable uptake characteristics. Planar imaging and organ distribution revealed a good tumor uptake of both, 99mTc- and 188Re-PSMA-GCK01 at 1 h and 3 h p.i. with low uptake in non-target organs. In patients, similar distribution patterns were observed for 99mTc-PSMA-GCK01 and 188Re-PSMA-GCK01 and also in comparison of Tc/Re-PSMA-GCK01 with 177Lu-PSMA-617. Conclusion: The novel ligand PSMA-GCK01 labels stable with 99mTc- and 188Re - both are generator based radionuclides – and, thus, provides access to on-demand labeling at reasonable costs. The preclinical evaluation of the compounds revealed favorable characteristics of the PSMA-targeted theranostic tandem. This result was further confirmed by a successful translation into first-in-human application. ER -