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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 NKtrans 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 NKtrans . A change in ΔsO2 and NKtrans 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.
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