Non-invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and evaluate novel therapeutic approaches. Non-invasive whole-body imaging using positron emission tomography (PET) provides critical insights into the in vivo characteristics of tissues at the molecular level in real-time. We present here a protocol for orthotopic HCC xenograft creation with and without hepatic artery ligation (HAL) to induce tumor hypoxia and the assessment of their tumor metabolism in vivo using [¹⁸F]Fluoromisonidazole ([¹⁸F]FMISO) and [¹⁸F]Fluorodeoxyglucose ([¹⁸F]FDG) PET/magnetic resonance (MR) imaging. Tumor hypoxia could be readily visualized using the hypoxia marker [¹⁸F]FMISO, and it was found that the [¹⁸F]FMISO uptake was higher in HCC mice that underwent HAL than in the non-HAL group, whereas [¹⁸F]FDG could not distinguish tumor hypoxia between the two groups. HAL tumors also displayed a higher level of hypoxia-inducible factor (HIF)-1α expression in response to hypoxia. Quantification of HAL tumors showed a 2.3-fold increase in [¹⁸F]FMISO uptake based on the standardized value uptake (SUV) approach.