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Photopharmacological Applications for Cherenkov Radiation Generated by Clinically Used Radionuclides.

ABSTRACT: 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 ⁶⁸Ga and ⁹⁰Y but not ¹⁸F 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 ⁹⁰Y, along with a non-specific compound decomposition for ⁶⁸Ga and partly for ⁹⁰Y. The findings suggest that the combination of a clinically employed radionuclide with an optimized photoresponsive agent could be beneficial for highly focused photopharmacological therapies.

SUBMITTER: Krebs M

PROVIDER: S-EPMC8396513 | biostudies-literature |

REPOSITORIES: biostudies-literature

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