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

We report a single-molecule radiotracer that can be labeled independently with ¹⁸ F-fluoride or radiometals (⁶⁴ Cu, ¹⁷⁷ Lu) 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 ¹⁸ F-, ⁶⁴ Cu- or ¹⁷⁷ Lu-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, ¹⁸ F-labeling capabilities for PET imaging with radiometalation for potential imaging and therapeutic applications.