Design and synthesis of a new conjugate of a tris(3-hydroxy-4-pyridinone) chelator (KC18) for potential use as gallium-68-labeled prostate-specific membrane antigen (PSMA) radiopharmaceutical

Prostate-specific membrane antigen (PSMA) is considered a significant target for the diagnosis and therapy of prostate cancer. 2-[3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid (DUPA) is a promising binding motif that has been proved to target PSMA successfully. 3-Hydroxy-4-pyridinone units containing multidentate bifunctional chelators could chelate gallium(III) at mild conditions effectively. In this letter, we combine DUPA with a tris (hydroxypyridinone) bifunctional chelator and get a novel precursor of gallium-68 radiopharmaceutical, DUPA beta-Ala-KC18. The synthesis, characterization of DUPA-beta-Ala-KC18 and the formation of its natural-abundance gallium(III) complex are presented. DUPA-beta-Ala-KC18 displayed a binding affinity to PSMA.

Automated summary

Prostate-specific membrane antigen (PSMA) is a significant target for prostate cancer diagnosis and therapy. The combination of DUPA with a multidentate bifunctional chelator successfully targets PSMA and forms a new precursor for gallium-68 radiopharmaceutical, DUPA beta-Ala-KC18. This novel compound displays binding affinity to PSMA.