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• W4319661477 abstract "<b>Introduction:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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." @default.
• W4319661477 created "2023-02-10" @default.
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• W4319661477 date "2023-02-09" @default.
• W4319661477 modified "2023-10-16" @default.
• W4319661477 title "PSMA-GCK01: A Generator-Based^99mTc/¹⁸⁸Re Theranostic Ligand for the Prostate-Specific Membrane Antigen" @default.
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• W4319661477 doi "https://doi.org/10.2967/jnumed.122.264944" @default.
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