Oxygen-enhanced and dynamic contrast-enhanced optoacoustic tomography provide surrogate biomarkers of tumour vascular function, hypoxia and necrosis.

Measuring the functional status of tumour vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatio-temporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that overcomes these challenges. By acquiring data at multiple wavelengths, OT can interrogate haemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumour vascular function, hypoxia and necrosis. We found that vascular maturity led to changes in vascular function that affected tumour perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumour and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumour hypoxia quantified ex vivo. Our findings indicate that OT may offer a significant advantage for localised imaging of tumour response to vascular targeted therapies when compared to existing clinical DCE methods.

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