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

Table 1 Reporter gene expression imaging with tumor-specific enhancers/promoters

Enhancer/promoter	Reporter gene(delivery method)	Imaging modality	Targeted tumor	Ref.
Survivin	hNIS (adenovirus)	Gamma camera	Ectopic xenograft	Huang et al[10]
			PC-3 (prostate cancer)
			HepG2 (hepatoma)
			A375 (melanoma)
	fLuc (adenovirus)	Bioluminescent imaging	Orthotopic xenograft	Ahn et al[11]
			McA-RH7777 (rat hepatoma)
Mucin-1	fLuc (adenovirus)	Bioluminescent imaging	Ectopic xenograft (metastasis)	Huyn et al[12]
			KPL-1 (breast cancer)
Hepatocarcinoma-intestine-pancreas (HIP)	NIS (adenovirus)	SPECT-CT	DEN-induced HCC (rat)	Hervé et al[13]
Prostate specific antigen (PSA)	fLuc/HSV1-sr39tk (adenovirus)	Bioluminescent imaging/ PET	Ectopic xenograft	Iyer et al[14]
			LNCaP (prostate cancer)	Jiang et al[15]
Carcinoembryonic antigen (CEA)	HSV1-tk (adenovirus)	Gamma camera	Ectopic xenograft	Qiao et al[16]
			MOD (murine breast cancer)
	hNIS (adenovirus)	Gamma camera	Ectopic xenograft	Spitzweg et al[17]
			TT (medullary thyroid cancer)
Progression elevated gene (PEG)-3	fLuc/HSV1-tk (plasmid)	Bioluminescent imaging/ SPECT-CT	Ectopic xenograft (metastasis)	Bhang et al[18]
			MeWo (melanoma)
			MDA-MB-231 (breast cancer)
Telomerase reverse transcriptase (TERT)	hNIS (plasmid)	SPECT-CT	Ectopic xenograft	Kim et al[19]
			Hep3B (hepatoma)
	GFP (lentivirus)	Fluorescence imaging	Ectopic xenograft	Yu et al[20]
			HepG2 (hepatoma)
			SGC-7901 (gastric cancer)
			SW480 (colon cancer)

fLuc: Firefly luciferase; GFP: Green fluorescent protein; hNIS: Human sodium iodide symporter; HSV1-TK: Herpes simplex virus type 1-thymidine kinase; PET: Positron emission tomography; SPECT-CT: Single-photon emission computed tomography-computed tomography.

Table 2 Experimental hepatocellular carcinoma animal models

Category		Inducing factor	Latency	Advantages	Disadvantages
Xenograft	Ectopic	Cancer cell line	Several weeks	Fast and easy modeling	Less clinical relevancy
	Orthotopic			Easy detection of tumorigenesis	Only reflect the characteristics of the selected cells
Carcinogen-induced		DEN	5-10 mo	More clinical relevancy	Lengthy time and high cost to model
Genetically engineered		HBV-derived	12-24 mo	Uncovering the molecular mechanisms of hepatocarcinogenesis	Difficult to detect tumorigenesis
		HCV-derived	12-24 mo	Closely mimic the pathophysiological features of human HCC
		Oncogene-derived	Several weeks

DEN: Diethylnitrosamine; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus.

Table 3 Reporter gene expression imaging by alpha-fetoprotein enhancer/promoter system

Tumor model	Mouse strain	Induction of HCC	Reporter gene	Delivery system	Injection route	Ref.
Xenograft	NOD/SCID	HuH-7 cells	hNIS	Adenovirus1	IV	Kim et al[56]
	BALB/c nude		TK/fLuc	Adenovirus1	IT	Park et al[57]
	NOD/SCID		fLuc	Adenovirus1	IV	Kim et al[58]
	BALB/c nude		hNIS	Plasmid2	-	Jin et al[52]
	CD-1 nude	HepG2 cells	hNIS	Adenovirus1	IT	Klutz et al[54]
	BALB/c nude		hNIS	Adenovirus1	IT	Ma et al[55]
	NMRI nude		hNIS	Plasmid2	-	Willhauck et al[53]
Carcinogen-induced	C57BL/6	DEN	fLuc	Adenovirus1	IV	Kim et al[58]
	FVB/N	DEN	TK/fLuc	Transgenesis3	-	Lu et al[59]
	C57BL/6	DEN	fLuc	Transgenesis3	-	Park et al[60]

¹Adenovirus: in vivo delivery of reporter gene;

²Plasmid: use of reporter gene transfected cells;

³Transgenesis: use of transgenic reporter mice. DEN: Diethylnitrosamine; fLuc: Firefly luciferase; hNIS: Human sodium iodide symporter; IT: Intratumoral injection; IV: Intravenous injection; NOD/SCID: Non-obese diabetic/severe combined immunodeficiency; TK: Thymidine kinase; HCC: Hepatocellular carcinoma.