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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.

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