New Bifunctional Chelator 3p-C-NEPA for Potential Applications in Lu(III) and Y(III) Radionuclide Therapy and Imaging

[Image: see text] We have developed structurally unique bifunctional chelators in the NETA, NE3TA, and DEPA series for potential radiopharmaceutical applications. As part of our continued research efforts to generate efficient bifunctional chelators for targeted radionuclide therapy and imaging of various diseases, we designed a scorpion-like chelator that is proposed to completely saturate the coordination spheres of Y(III) and Lu(III). We herein report the synthesis and evaluation of a new chelator (3p-C-NEPA) with 10 donor groups for complexation with β-emitting radionuclides (90)Y(III), (86)Y(III), and (177)Lu(III). The chelator was synthesized and evaluated for radiolabeling kinetics with the readily available radioisotopes (90)Y and (177)Lu, and the corresponding (90)Y or (177)Lu-radiolabeled complexes were evaluated for in vitro stability in human serum and in vivo complex stability in mice. The new chelator rapidly bound (90)Y or (177)Lu and formed a stable complex with the radionuclides. The new chelator 3p-C-NEPA radiolabeled with either (90)Y or (177)Lu remains stable in human serum without dissociation for 10 days. (177)Lu-labeled 3p-C-NEPA produced a favorable in vivo biodistribution profile in normal mice.