In Vivo Photoactivation Without Light: Use of Cherenkov Radiation to Overcome the Penetration Limit of Light

The poor tissue penetration of visible light has been a major barrier for optical imaging, photoactivatable conversions, and photodynamic therapy for in vivo targets with depths beyond 10 mm. In this report, as a proof-of-concept, we demonstrated that a positron emission tomography (PET) radiotracer, 2-deoxy-2-[F-18]fluoro-d-glucose ((18)FDG), could be used as an alternative light source for photoactivation. We utilized (18)FDG, which is a metabolic activity-based PET probe, as a source of light to photoactivate caged luciferin in a breast cancer animal model expressing luciferase. Bioluminescence produced from luciferin allowed for the real-time monitoring of Cherenkov radiation-promoted uncaging of the substrate. The proposed method may provide a very important option for in vivo photoactivation, in particular for activation of photosensitizers for photodynamic therapy and eventually for combining radioisotope therapy and photodynamic therapy.