In vitro irradiation of doxorubicin with F-18-FDG Cerenkov radiation and its potential application as a theragnostic system

摘要

Doxorubicin (DOX), an effective chemotherapeutic agent, has a wide excitation band centred at 480 nm. Cerenkov radiation (CR) is considered an internal light source in photodynamic therapy (PDT). DOX could be photoactivated by CR and thus, enhancing its cytotoxicity. In this work, F-18-FDG was used to evaluate the effect of Cerenkov radiation on DOX, in comparison to irradiation with a 450-nm laser beam, in terms of ROS production. The production of O- 1(2) and O-2*(-) reactive species during DOX irradiation was detected indirectly by ABMA and DCPIP bleaching, respectively. The cytotoxic effect of the DOX /F-18-FDG CR system was evaluated in the T47D breast cancer cell line. The irradiation of DOX produced( 1)O(2) and O-2*(-) species using both F-18-FDG CR and a 450-nm laser beam. The majority reactive species produced in both cases was O-1(2); a favourable result, given the greater cytotoxicity of this species. The viability of T47D cells in presence of DOX (5 nM), F-18-FDG (37.5 mu Ci) and DOX (5 nM)/F-18-FDG (37.5 mu Ci) was (86 +/- 9)%, (84 +/- 8)% and (64 +/- 5)%, respectively; these results suggest a synergistic cytotoxic effect derived from the cytotoxic activity of DOX and its photoactivation by F-18-FDG CR. It is worth noting that the system could be optimized in terms of DOX concentration and F-18-FDG activity for better results. Due to the fact that F-18-FDG is widely used in nuclear imaging, the DOX/F-18-FDG system also possesses theragnostic characteristics. Thus, in this work, it is demonstrated that DOX can be used in a dual therapy system based on chemotherapy-PDT when F-18-FDG CR is used as a DOX excitation source.