Non-invasive monitoring of the therapeutic response in sorafenib-treated hepatocellular carcinoma based on photoacoustic imaging.

Abstract

We investigated the changes of tissue oxygen saturation (sO₂) in sorafenib-treated HCC (hepatocelluar carcinoma) mouse models using photoacoustic imaging (PI). Nude 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 (R_E) and therapeutic response were analysed by fluorescence imaging and histologic analysis. Sorafenib 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. Sorafenib 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. • Hypoxia is a characteristic feature of the tumour microenvironment • It is important to monitor sO ₂ in HCC during sorafenib treatment • PI is useful for non-invasive monitoring of sO ₂ in HCC. • ΔsO ₂ in HCC showed a significantly correlation with tumour response.