Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects

Table 1 Positron emission tomography for intrahepatic or extrahepatic hepatocellular carcinoma

Isotopes	Half-life	Radiotr-acer	Year	First author	No. of patients	Study design	Intrahepatic		Extrahepatic		Related notable findings
							Sensiti-vity	Specifi-city	Sensiti-vity	Specifi-city
18F	110 min	18F-FDG	2019	Lee et al[11]	-	Review	0.36-0.70	NA	NA	NA	18F-FDG PET has demonstr-ated a higher sensitivity for detecting extrahepa-tic metastasis compared to primary HCC
			2012	Hossein Jadvar[29]		Review	NA	0.91	NA	NA
			2012	Lin et al[89]		Meta-analysis	NA	NA	0.77	0.98
		18F-FCH	2014	Bieze et al[21]	30	Prospective; single-center	0.88	1.0	1.0	1.0	18F-FCH shows additional value in the assessment of intra- and extrahepa-tic diseases
11C	20 min	11C-ACT	2009	Hwang et al[27]	13	Prospective	0.83	NA	0.77	NA	11C increases the sensitivity in the detection of HCC lesions of more than 10 mm
		11C-CHOL	2016	Castilla-Lièvre et al[71]	28	Prospective; single-center	0.67	NA	NA	NA	Combining 18F-FDG with 11C-CHOL could be useful for clinicians in the manage-ment of HCC patients

HCC: Hepatocellular carcinoma; NA: Not available;

¹⁸F-FDG: 2-deoxy-2-(¹⁸F)fluoro-D-glucose; ¹⁸F-FCH: ¹⁸F-fluorocholine;

¹¹C-ACT: 11C-acetate; ¹¹C-CHOL: ¹¹C-choline.

Table 2 Positron emission tomography in animal experiments of hepatocellular carcinoma

Isotopes	Half-life	Radiotracer	Year	First author	Animal models	Related notable findings	Limitations
18F	110 min	18F-FPGLU	2017	Sun et al[19]	Tumor-bearing mice (HCC SMCC-7721)	Radiochemical purity is higher than 95% with a specific activity of 30-40 GBq/μmol	Unstable in plasma, tumor, and urine
						Stable in vitro
						High uptake and retention in tumor
64Cu	12.7 h	64CuCl2	2011	Lièvre et al[71]	Athymic mice bearing extrahepatic HCC xenografts	Increased 64Cu radioactivity is well visualized	Abundant physiological distribution in liver
						Useful for detection of intracranial HCC metastasis
68Ga	68 min	68Ga-NGR	2017	Gao et al[32]	Tumor-bearing mice (HCC SMCC-7721)	68Ga-NGR could visualize CD13-positive tumors	The uptake performance of 68Ga-NGR for poorly differentiated HCC needs further investigation
						68Ga-NGR uptake is significantly higher than that of 18F-FDG in well-differentiated HCC xenografts
89Zr	78.4 h	89Zr-αGPC3	2014	Sham et al[79]	HepG2 tumor-bearing mice	Excellent specificity	Long half-life in the blood, leading to suboptimal imaging pharmacokinetics, poorer tumor penetration, and increased immunogenicity due to relatively large size and intact Fc regions
						Even smaller tumors (<1 mm) are able to be identified
		89Zr-αGPC3-F(ab′)2	2014	Sham et al[80]	HepG2 tumor-bearing mice	Significantly reduces blood circulation time	Potential risk of fragment concentration in the kidneys, leading to organ dysfunction
						Lower background liver uptake allows for early imaging
		89Zr-DFO-1G12	2014	Yang et al[81]	HepG2 tumor-bearing mice	Specifically taken up by GPC3-positive HCC xenografts regardless of GPC3 expression levels	This probe should be further validated using a humanized anti-GPC3 antibody
						High tumor-to-liver ratio
		89Zr-Df-YY146-ZW800	2016	Hernandez et al[82]	HepG2 tumor-bearing mice	Excellent CD146-affinity, specificity, and stability	Bone-displaying PET signal is not matched by NIRF
						Both PET and NIRF imaging are achieved

HCC: Hepatocellular carcinoma; PET: Positron emission tomography;

¹⁸F-FPGLU: N-(2-¹⁸F-fluoropropionyl)-L-glutamate;

⁶⁸Ga-NGR: ⁶⁸Ga-labeled asparagine-glycine-arginine;

⁸⁹Zr-αGPC3: ⁸⁹Zr-anti glypican-3; ⁸⁹Zr-αGPC3-F(ab’)2: ⁸⁹Zr-anti glypican-3-F(ab’)2; ⁸⁹Zr-DFO-1G12: ⁸⁹Zr-desferrioxamine-1G12; ⁸⁹Zr-Df-YY146-ZW800: ⁸⁹Zr- deferoxamine-YY146-ZW800; NIRF: Near-infrared fluorescence.