Toward 18F-Labeled Theranostics: A Single Agent that Can Be Labeled with 18F, 64Cu, or 177Lu

We report a single-molecule radiotracer that can be labeled independently with F-18-fluoride or radiometals (Cu-64, Lu-177) in a single step. A prostate-specific membrane antigen (PSMA)-targeting ligand, armed with both an organotrifluoroborate and a metal-chelator (DOTA), was designed to optionally afford F-18-, Cu-64- or Lu-177-labeled products that were injected into mice bearing prostate cancer (LNCaP) xenografts. PET/CT images and ex vivo biodistribution data show high, specific tumor uptake irrespective of which radionuclide is used, thereby demonstrating a new approach to combining, in a single molecule, F-18-labeling capabilities for PET imaging with radiometalation for potential imaging and therapeutic applications.