Evaluations of radiotherapy in small animal models of pancreatic cancer with Oxygen Enhanced–Dynamic Contrast Enhanced Multispectral Optoacoustic Tomography (OE-DCE MSOT)

Tumor hypoxia causes resistance to radiotherapy. A non-invasive imaging method is needed to quantitatively measure tumor hypoxia to predict radiotherapy response before starting treatment. Furthermore, radiotherapy can damage blood vessels, which can reduce vascular perfusion and oxygen delivery. We have developed Oxygen Enhanced – Dynamic Contrast Enhanced Multispectral Optoacoustic Tomography (OE-DCE MSOT) that can evaluate hypoxia and vascular perfusion in a single scan session. OE MSOT measures oxygen saturation with medical grade air (%sO2^air using 21% O2) breathing gas and 100% breathing gas (%sO2^O2), and the “available oxygen capacity” (ΔsO2) that is the difference between %sO2^air and %sO2^air. DCE MSOT uses the normalized pharmacokinetics profile of an exogenous contrast agent in a tumor to calculate NK^trans and kep, which indicate the wash-in and wash-out vascular perfusion rates, respectively. We have shown that our DCE MSOT methodology avoids the problem of variable fluence within in vivo tissues. We applied OE-DCE MSOT to study the effect of radiotherapy on three tumor models that have different levels of vascular perfusion and hypoxia. Our results showed that %sO2^air, %sO2^O2, ΔsO2 identified normoxic, mildly hypoxic, and hypoxic models, which was related to the high-to-low status of vascular perfusing as measured with NK^trans. A change in ΔsO2 and NK^trans indicated early response to radiotherapy. These results demonstrate the advantages of OE-DCE MSOT for simultaneously evaluating tumor hypoxia and vascular perfusion before and soon after treatment.