Photopharmacological Applications for Cherenkov Radiation Generated by Clinically Used Radionuclides

Translational photopharmacological applications are limited through irradiation by light showing wavelengths within the bio-optical window. To achieve sufficient tissue penetration, using wavelengths >500 nm is mandatory. Nevertheless, the majority of photopharmacological compounds respond to irradiation with more energetic UV light, which shows only a minor depth of tissue penetration in the µm range. Thus, we became interested in UV light containing Cherenkov radiation (CR) induced as a by-product by clinically employed radionuclides labeling specific tissues. Therefore, CR may be applicable in novel photopharmacological approaches. To provide evidence for the hypothesis, we verified the clinically established radionuclides (68)Ga and (90)Y but not (18)F in clinically used activities to be capable of generating CR in aqueous solutions. We then investigated whether the generated CR was able to photoactivate the caged kinase inhibitor cagedAZD5438 as a photoresponsive model system. Herein, 21% uncaging of the model system cagedAZD5438 occurred by incubation with (90)Y, along with a non-specific compound decomposition for (68)Ga and partly for (90)Y. The findings suggest that the combination of a clinically employed radionuclide with an optimized photoresponsive agent could be beneficial for highly focused photopharmacological therapies.