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AbstractPurposeWe investigated the changes of tissue oxygen saturation (sO2) in sorafenib-treated HCC (hepatocelluar carcinoma) mouse models using photoacoustic imaging (PI).Materials and MethodsNude mice, implanted with human HCC (HepG2-RFP) cells in the liver, were randomised to the sorafenib-treated group (n = 21) or the control group (n = 20). Tumour volume and sO2 were measured by PI at baseline and then one week later, and radiant efficiency (RE) and therapeutic response were analysed by fluorescence imaging and histologic analysis.ResultsSorafenib was effective in treating HCC by evaluating necrotic fraction, apoptosis index, and microvessel density (MVD). One week after treatment, the sO2 of HCC and residual healthy liver tissue decreased, and the hypoxia inducible factor-1α (HIF-1α) protein expression of HCC increased, correlating with the apoptosis index. The ΔsO2 in HCC showed a significantly positive correlation with the necrotic fraction and the apoptosis index of tumour and a negative correlation with the MVD of tumour.ConclusionSorafenib treatment results in changes of sO2 in HCC and liver parenchyma and induces the accumulation of HIF-1α by hypoxic environment. sO2 as measured by PI, can be a useful marker for non-invasive monitoring of the therapeutic response in orthotopic HCC mouse models.Key Points• Hypoxia is a characteristic feature of the tumour microenvironment • It is important to monitor sO2in HCC during sorafenib treatment • PI is useful for non-invasive monitoring of sO2in HCC.• ΔsO2in HCC showed a significantly correlation with tumour response.