Here, we assess the capabilities of photoacoustic imaging (PAI) biomarkers to shed light into perfusion-limited hypoxia, a key driver of tumor malignancy. Using two breast cancer xenograft models, we found that photoacoustic tomography could detect higher fluctuations in oxygen saturation (sO2MSOT) in models with higher disease aggressiveness, supported by an overall lower sO2MSOT and greater spatial heterogeneity in sO2MSOT. Photoacoustic mesoscopy revealed differences in vascular architecture and perfusion dynamics between the models. The results were validated using immunohistochemistry and RNA sequencing, highlighting the potential of PAI to provide non-invasive insight on dynamic phenomena associated with perfusion-limited hypoxia in vivo.
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