Activating TiO2 Nanoparticles: Gallium-68 Serves as a High-Yield Photon Emitter for Cerenkov-Induced Photodynamic Therapy

The classical photodynamic therapy (PDT) requires external light to activate photosensitizers for cancer treatment. However, limited tissue penetration of light has been a long-standing challenge for PDT to cure malignant tumors in deep tissues. Recently, Cerenkov radiation (CR) emitted by radiotracers such as 18F-fluorodeoxyglucose (18F-FDG) has become an alternative and promising internal light source. Nevertheless, fluorine-18 (F-18) only releases 1.3 photons per decay in average; consequently, injection dose of F-18 goes beyond 10–30 times more than usual to acquire therapeutic efficacy because of its low Cerenkov productivity. Gallium-68 (Ga-68) is a favorable CR source owing to its ready availability from generator and 30-time higher Cerenkov productivity. Herein, we report, for the first time, the use of Ga-68 as a CR source to activate dextran-modified TiO2 nanoparticles (D-TiO2 NPs) for CR-induced PDT. Compared with 18F-FDG, 68Ga-labeled bovine serum albumin (68Ga-BSA) inhibited the growth of 4T1...