64Cu-Doped PdCu@Au Tripods: A Multifunctional Nanomaterial for Positron Emission Tomography and Image-Guided Photothermal Cancer Treatment

This article reports a facile synthesis of radiolabeled PdCu@Au core-shell tripods for use in positron emission tomography (PET) and image-guided photothermal cancer treatment by directly incorporating radioactive Cu-64 atoms into the crystal lattice. The tripod had a unique morphology determined by the PdCu tripod that served as a template for the coating of Au shell, in addition to well-controlled specific activity and physical dimensions. The Au shell provided the nanostructure with strong absorption in the near-infrared region and effectively prevented the Cu and Cu-64 atoms in the, core from oxidization and dissolution. When conjugated with D-Ala(1)-peptide T-amide (DAPTA), the core shell tripods showed great enhancement in targeting the C-C chemokine receptor 5 (CCRS), a newly identified theranostic target up-regulated in triple negative breast cancer (TNBC). Specifically, the CCRS-targeted tripods with an arm length of about 45 nm showed 2- and 6-fold increase in tumor-to-blood and tumor-to-muscle uptake ratios, respectively, relative to their nontargeted counterpart in an orthotopic mouse 4T1 TNBC model at 24 h postinjection. The targeting specificity was further validated via a competitive receptor blocking study. We also demonstrated the use of these targeted, radioactive tripods for effective photothermal treatment in the 4T1 tumor model as guided by PET imaging. The efficacy of treatment was confirmed by the significant reduction in tumor metabolic activity revealed through the use of P-18-fluorodeoxyglucose PET/CT imaging. Taken together, we believe that the Cu-64-doped PdCu@Au tripods could serve as a multifunctional platform for both PET imaging and image-guided photothermal cancer therapy.