Nkov radiation to locally excite the PSCerenkov radiation has been proposed to generate light in deep tissues using ionizing radiation. Cerenkov emission is observed when charged particles, e.g. electrons or positrons, travel faster than the phase velocity of light in a given medium. Because there is a minimum velocity associated with this kind of radiation, there is also a minimum energy value required for these particles to be classified as Cerenkov. Thus, Cerenkov radiation can be generated either by + or – emitter radioisotopes such as those used for positron emission tomography (PET) or X-ray based radiotherapy, which induce an electromagnetic cascade containing high-energy charged particles that interact with matter. The spectrum of Cerenkov emission is broad, is centered in the near ultra-violet range and can overlap with many PS excitation spectra (Fig. 5B2). In addition, the radionuclides and ionizing radiation used for radiotherapy can be used to generate Cerenkovhttp://www.thno.orgTheranostics 2016, Vol. 6, Issueemission making it particularly attractive for deep-tissue PDT. Although this approach is still relatively under-explored, two promising studies have been recently published. First, Axelsson et al. not only demonstrated that a measurable Cerenkov emission was produced in a water phantom following irradiation by X-rays (6-18MV) or electrons (6-18 MeV) delivered by a clinically used linear accelerator, but also that this Cerenkov emission was able to activate PpIX in solution [101]. This proof of concept demonstrated the potential role of Cerenkov radiation to induce PS excitation and PDT in deep tissues. More recently, Kotagiri et al. demonstrated that 64Cu radionuclide, usually used as a PET radiotracer and characterized by a high positron emission and fast decay, could induce Cerenkov radiation and excite TiO2 NPs that act as oxygen independent PS. In addition to demonstrating efficient cell killing in vitro, the authors presented in vivo experiments showing complete eradication of the tumor when NPs were combined with the 64Cu radionuclide, GS-4059 site whereas tumors were unaffected in all the treatment control conditions [102]. Even though the number of published studies remains low, Cerenkov radiation seems to be a promising approach to activate the PS in deep tissues, either by using ionizing radiations utilized for RT (X-rays) or diagnostic purposes (radiotracers).showed similar energy transfer properties post excitation with X-ray irradiation. Most of these “proof of concept” studies are restricted to optical measurements (emission spectra, fluorescence decay, 1O chemical probes fluorescence properties) [105, 2 106] or in vitro experiments demonstrating reduction in viability due to nanoscintillator based PDT. For example, Abliz et al. reported a reduction in viability of human glioblastoma cells, from 80 to 10 , when get MK-1439 micrometric gadolinium oxysulfide particles were combined with Photofrin II and irradiated with X-rays [107]. In order to help design useful nanoscintillator/PS conjugates with optimal size or composition that can induce cytotoxic effects in deep tissue following X-rays irradiation, it is necessary to better understand and characterize the underlying mechanisms. In this spirit, a study based on time-resolved spectroscopic measurements of terbium oxide nanoparticles (Tb2O3@SiO2 NPs) conjugated to a porphyrin PS revealed an energy transfer that occurs from the nanoscintillator to the PS, mainly as a non-radiat.Nkov radiation to locally excite the PSCerenkov radiation has been proposed to generate light in deep tissues using ionizing radiation. Cerenkov emission is observed when charged particles, e.g. electrons or positrons, travel faster than the phase velocity of light in a given medium. Because there is a minimum velocity associated with this kind of radiation, there is also a minimum energy value required for these particles to be classified as Cerenkov. Thus, Cerenkov radiation can be generated either by + or – emitter radioisotopes such as those used for positron emission tomography (PET) or X-ray based radiotherapy, which induce an electromagnetic cascade containing high-energy charged particles that interact with matter. The spectrum of Cerenkov emission is broad, is centered in the near ultra-violet range and can overlap with many PS excitation spectra (Fig. 5B2). In addition, the radionuclides and ionizing radiation used for radiotherapy can be used to generate Cerenkovhttp://www.thno.orgTheranostics 2016, Vol. 6, Issueemission making it particularly attractive for deep-tissue PDT. Although this approach is still relatively under-explored, two promising studies have been recently published. First, Axelsson et al. not only demonstrated that a measurable Cerenkov emission was produced in a water phantom following irradiation by X-rays (6-18MV) or electrons (6-18 MeV) delivered by a clinically used linear accelerator, but also that this Cerenkov emission was able to activate PpIX in solution [101]. This proof of concept demonstrated the potential role of Cerenkov radiation to induce PS excitation and PDT in deep tissues. More recently, Kotagiri et al. demonstrated that 64Cu radionuclide, usually used as a PET radiotracer and characterized by a high positron emission and fast decay, could induce Cerenkov radiation and excite TiO2 NPs that act as oxygen independent PS. In addition to demonstrating efficient cell killing in vitro, the authors presented in vivo experiments showing complete eradication of the tumor when NPs were combined with the 64Cu radionuclide, whereas tumors were unaffected in all the treatment control conditions [102]. Even though the number of published studies remains low, Cerenkov radiation seems to be a promising approach to activate the PS in deep tissues, either by using ionizing radiations utilized for RT (X-rays) or diagnostic purposes (radiotracers).showed similar energy transfer properties post excitation with X-ray irradiation. Most of these “proof of concept” studies are restricted to optical measurements (emission spectra, fluorescence decay, 1O chemical probes fluorescence properties) [105, 2 106] or in vitro experiments demonstrating reduction in viability due to nanoscintillator based PDT. For example, Abliz et al. reported a reduction in viability of human glioblastoma cells, from 80 to 10 , when micrometric gadolinium oxysulfide particles were combined with Photofrin II and irradiated with X-rays [107]. In order to help design useful nanoscintillator/PS conjugates with optimal size or composition that can induce cytotoxic effects in deep tissue following X-rays irradiation, it is necessary to better understand and characterize the underlying mechanisms. In this spirit, a study based on time-resolved spectroscopic measurements of terbium oxide nanoparticles (Tb2O3@SiO2 NPs) conjugated to a porphyrin PS revealed an energy transfer that occurs from the nanoscintillator to the PS, mainly as a non-radiat.