Oxygels: Tunable Phosphorescent Hydrogels for Cherenkov-Excited Luminescence Imaging (CELI) of Oxygen

We present a family of phosphorescent hydrogels, termed Oxygels, for local deep-tissue oxygen sensing by Cherenkov-excited luminescence imaging (CELI). Oxygels comprise dendritic phosphorescent probes covalently bound within a polyethyleneglycol (PEG) matrix held together by an optically neutral dendritic cross-linker. Covalent attachment of the phosphorescent probe within the matrix prevents its leaching from the gel. Changing the size/generation of the dendrimer surrounding the phosphorescent center enables tuning of Oxygel sensitivity, while varying the ratio between the probe and neutral cross-linker helps to optimize Oxygel performance. Upon implantation into tissue, Oxygels induced only a moderate initial foreign body response with minimal macrophage recruitment. The performance of the Oxygels in CELI was evaluated using electron pulses from a linear accelerator (linac) for Cherenkov excitation. Robust phosphorescence decays were detected from Oxygels implanted subcutaneously or abdominally in mice in vivo using peripheral detectors upon excitation by clinical radiation doses (up to 10 Gy) delivered in FLASH mode. The resulting decay time constants provide quantitative information about tissue oxygenation at the site of Oxygel implantation.