PSMA-GCK01: A Generator-Based <sup>99m</sup>Tc/<sup>188</sup>Re Theranostic Ligand for the Prostate-Specific Membrane Antigen.
Where this comes from
- Record sourced from PubMed, PMID 36759199.
- Also identified by DOI 10.2967/jnumed.122.264944 and PMC identifier 10315696.
- Licence recorded as CC BY.
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Abstract
Prostate-specific membrane antigen (PSMA) theranostics have been introduced with <sup>68</sup>Ga and <sup>177</sup>Lu, the most used radionuclides. However, <sup>188</sup>Re is a well-known generator-based therapeutic nuclide that completes a theranostic tandem with <sup>99m</sup>Tc and may offer an interesting alternative to the currently used radionuclides. In the present work, we aimed at the development of a PSMA-targeted <sup>99m</sup>Tc/<sup>188</sup>Re theranostic tandem. <b>Methods:</b> The ligand HYNIC-iPSMA was chosen as the lead structure. Its HYNIC chelator has limitations for <sup>188</sup>Re labeling and was replaced by mercaptoacetyltriserine to obtain PSMA-GCK01, a precursor for stable <sup>99m</sup>Tc and <sup>188</sup>Re labeling. <sup>99m</sup>Tc-PSMA-GCK01 was used for in vitro evaluation of the ligand and comparison with <sup>99m</sup>Tc-EDDA/HYNIC-iPSMA. Planar imaging using <sup>99m</sup>Tc-PSMA-GCK01 and organ biodistribution with <sup>188</sup>Re-PSMA-GCK01 were performed using LNCaP tumor-bearing mice. Finally, the theranostic tandem was applied for imaging and therapy in 3 prostate cancer patients in compassionate care. <b>Results:</b> Efficient radiolabeling of PSMA-GCK01 with both radionuclides was demonstrated. Cell-based assays with <sup>99m</sup>Tc-PSMA-GCK01 versus <sup>99m</sup>Tc-EDDA/HYNIC-iPSMA revealed comparable uptake characteristics. Planar imaging and organ distribution revealed good tumor uptake of both <sup>99m</sup>Tc-PSMA-GCK01 and <sup>188</sup>Re-PSMA-GCK01 at 1 and 3 h after injection, with low uptake in nontarget organs. In patients, similar distribution patterns were observed for <sup>99m</sup>Tc-PSMA-GCK01 and <sup>188</sup>Re-PSMA-GCK01 and in comparison with <sup>177</sup>Lu-PSMA-617. <b>Conclusion:</b> The ligand PSMA-GCK01 labels stably with <sup>99m</sup>Tc and <sup>188</sup>Re, both generator-based radionuclides, and thus provides access to on-demand labeling at reasonable costs. Preclinical evaluation of the compounds revealed favorable characteristics of the PSMA-targeted theranostic tandem. This result was confirmed by successful translation into first-in-humans application.
Medical subject headings
- Precision Medicine
- Prostatic Neoplasms