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 (sO(2)) 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 sO(2) 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 sO(2) of HCC and residual healthy liver tissue decreased, and the hypoxia inducible factor-1 alpha (HIF-1 alpha) protein expression of HCC increased, correlating with the apoptosis index. The Delta sO(2) 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 sO(2) in HCC and liver parenchyma and induces the accumulation of HIF-1 alpha by hypoxic environment. sO(2) as measured by PI, can be a useful marker for non-invasive monitoring of the therapeutic response in orthotopic HCC mouse models. aEuro cent Hypoxia is a characteristic feature of the tumour microenvironment aEuro cent It is important to monitor sO (2) in HCC during sorafenib treatment aEuro cent PI is useful for non-invasive monitoring of sO (2) in HCC. aEuro cent Delta sO (2) in HCC showed a significantly correlation with tumour response.