Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene’s expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.

Keywords: Alpha-fetoprotein, Hepatocellular carcinoma, Molecular imaging, Reporter gene, Tumor-specific enhancer/promoter

Core tip: It is essential to establish an appropriate animal model of hepatocellular carcinoma (HCC) for monitoring the disease progression and evaluating therapeutic interventions with anticancer drugs. Reporter gene-based molecular imaging can elucidate tumor-specific events or processes through acquisition of images of reporter gene expression driven by tumor-specific enhancers/promoters. In this paper, we describe the advantages and disadvantages of various animal models of HCC and present images of in vivo reporter gene expression controlled by alpha-fetoprotein enhancer/promoter in the various HCC animal models.