TY - JOUR T1 - Activating TiO<sub>2</sub> Nanoparticle: Gallium-68 Serves As A High-Yielded Photon Emitter for Cerenkov Induced Photodynamic Therapy JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1247 LP - 1247 VL - 59 IS - supplement 1 AU - Dongban Duan AU - Hui Liu AU - Yang Xu AU - Yuxiang Han AU - Mengxin Xu AU - Zhibo Liu Y1 - 2018/05/01 UR - http://jnm.snmjournals.org/content/59/supplement_1/1247.abstract N2 - 1247Objectives: The classical photodynamic therapy (PDT) requires external light to activate photosensitizers to treat cancer. But the poor tissue penetration of light has greatly limited its clinical application. In recent, Cerenkov radiation (CR) emitted by radiotracers such as 18F-FDG has become an alternative and promising internal light source. Nevertheless, in average fluorine-18 (F-18) only releases 1.3 photons per decay, consequently injection dose of F-18 goes beyond 10-30 times more than usual to acquire therapeutic efficacy. In contrast, Gallium-68 (Ga-68) emits 33.9 photons per decay, which is 30-times higher than F-18. Herein, we report as the first time of using Ga-68 to be a CR source to activate dextran modified TiO2 nanoparticles (D-TiO2 NPs) for depth-independent PDT, and promising results have been achieved. Methods: Dextran modified TiO2 nanoparticles (D-TiO2 NPs) were prepared and characterized by TEM, XRD, XPS, FTIR, DLS and TG. Cellular uptake of D-TiO2 NPs was investigated by flow cytometry and confocal microscopy. In vitro study was performed in mouse breast cancer 4T1 cells, and cell-uptake studies, cell-viability assays and γ-H2AX immunofluorescence analysis were conducted. In vivo CR induced PDT cancer treatment was performed in 4T1 breast tumor model. PET imaging was recorded on a micro-PET/CT scanner. Results: Elongated rhombic-shaped TiO2 colloidal with high photocatalytic efficiency was confirmed as a single-crystalline anatase structure. D-TiO2 NPs contained approximately 12% dextran in weight percent and exhibited high cellular uptake and low cytotoxicity to 4T1 cells. The total CR photons generated by intracellular 68Ga-BSA were approximately 4.5 times than that of 18F-FDG (Figure B), suggesting that 68Ga-BSA could give better performance in PDT than 18F-FDG on CR induced PDT. As showed in Figure C, the tumor volumes of mice treated by 68Ga-BSA and D-TiO2 NPs were significantly inhibited, whereas no significant difference in tumor volumes was found between the control group and other treatment groups. Moreover, the mice in the treated groups (68Ga-BSA &amp; D-TiO2 NPs) showed significantly prolonged survival time compared to the other control groups (Figure D). Conclusion: D-TiO2 NPs as UV photosensitizer for CR induced PDT were prepared, and exhibited high cellular uptake and low cytotoxicity to 4T1 cells. Ga-68 demonstrated significantly better tumor suppression than F-18 against 4T1 cancer cells both in vitro and in vivo, suggesting that Gallium-68 was very attractive for depth-independent cancer therapy without using any external light source. ER -