Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer

Table 1 Imaging techniques and contrast agents applied for the detection of woodchuck hepatocellular carcinoma

Imaging technique	Contrast agent	Brand name	Ref.
Ultrasonography	Air-filled albumin microspheres		[195]
	Cyanacrylate polymer microparticles	SHU563A	[196]
	Dodecafluoropentane emulsion	EchoGen	[197,198]
	Galactose microparticles/palmitic acid	Levovist	[199-201]
	Perflexane-filled lipid microspheres	Imagent	[202]
	Perfluoropropane-filled albumin microspheres	Optison/FS069	[95,200,201,203,204]
Scintigraphy	99mTc-sulfur colloid		[205]
Positron-emission tomography	[1-11C]acetate		[206-208]
	[1-14C]acetate		[207]
	[N-methyl-11C]choline		[206,209,210]
	[18F]clofarabine		[211]
	[18F]fluoro-ethylcholine		[210]
	Anti-1-amino-3-[18F]fluoro-cyclobutyl-1-carboxylic acid		[212]
	2-deoxy-2-[18F]fluoro-D-glucose		[208,209,213]
	6-deoxy-6[18F]fluoro-D-glucose		[206,209,210]
	L-[S-methyl-11C]methionine		[212]
	3-deoxy-3-[18F]fluoro-thymidine		[214]
Magnetic resonance imaging	Gadolinium	Gadavist or Omniscan	[157,179,185]
	Gadopentetate dimeglumine	Magnevist	[158,189]
	Iron oxide		[215,216]
Computed tomography	Biodegradable radiopaque fiducial markers based on polymers and iodine	Ioversol, Isovue-370, Optiray300, or Optiray350	[152,153,159,186,206]
	Diatrizoic acid	Angiografin	[190]
	Meglumine iotroxate	Biliscopin	[151]
	Iohexol	Omnipaque or Omnipaque350	[157,188]

Table 2 Nucleos(t)ide analogs evaluated in woodchucks for safety and antiviral efficacy against hepatitis B virus

Antiviral drug	Abbreviation	Brand name	Ref.
Adefovir dipivoxil	ADV	Hepsera	[217-219]
Clevudine1	CLV or L-FMAU	Levovir and Revovir	[172,220-222]
Emtricitabine	FTC	Coviracil	[219,221,223,224]
Entecavir1	ETV	Baraclude	[171,225-228]
Lamivudine1	LAM or 3TC	Epivir	[164,165,194,219,229]
Telbivudine	LdT	Tyzeka	[230-232]
Tenofovir alafenamide	TAF	Vemlidy	[233]
Tenofovir disoproxil fumarate	TDF	Viread	[219]
Valtorcitabine	LdC		[230-232]

¹Long-term treatment with these drugs delayed hepatocellular carcinoma (HCC) onset and extended HCC-free survival in woodchucks. See text for more details.

Table 3 Immunomodulators evaluated in woodchucks for safety and antiviral efficacy against hepatitis B virus

Immunomodulator	Compound name	Brand name	Ref.
IFN-α			[192,226,228,229]
RIG-I/NOD2 agonist	SB 9200	Inarigivir	[227]
TLR7 agonist	GS-96201	Vesatolimod	[173]
	APR002		[225]
	RG7854		[38]
TLR8 agonist	GS-9688	Selgantolimod	[174]
TLR9 agonist	CpG-ODN		[234]
TLR9-dependent and -independent pathways	AIC649		[235]
	JVRS-1002		[175]
Viral gene expression inhibitor	RG7834		[226]
Immune checkpoint inhibitor	Anti-PD-L1		[236]

¹Treatment delayed hepatocellular carcinoma onset in woodchucks.

²Treatment inhibited formation of new liver tumors in woodchucks.

See text for more details. Anti-PD-L1: Antibody against programmed death-ligand 1; CpG-ODN: CpG oligodeoxynucleotide, a short single-stranded synthetic DNA molecule containing unmethylated deoxycytosine-deoxyguanosine (CpG) motifs; IFN-α: Interferon alpha; JVRS-100: Complex of non-coding plasmid DNA and cationic liposomes; NOD2: Nucleotide-binding oligomerization domain-containing protein 2; RIG-I: Retinoic acid-inducible gene I; TLR: Toll-like receptor.