title: Evaluation of diethylnitrosamine- or hepatitis B virus X gene-induced hepatocellular carcinoma with 18F-FDG PET/CT: a preclinical study.
abstract: The aim of this study was to evaluate whether the development of hepatocellular carcinoma (HCC) in murine models resembles tumor progression in humans, using non‑invasive molecular imaging methods. Murine HCC models were generated by treating mice with diethylnitrosamine (DEN) or by the transgenic expression of hepatitis B virus X (HBx) protein (HBx-Tg model). Tumor development was detected using 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI). The histopathological changes and expression of glucose transporter 1 (Glut1) and hexokinase 2 (HK2) were evaluated using hematoxylin and eosin and immunohistochemical staining, respectively. Tumor lesions as small as 1 mm in diameter were detected by MRI. Tumor development was monitored using 18F-FDG PET/CT at 6.5‑10 months after DEN treatment or 11‑20 months after birth of the HBx-Tg model mice. A correlation study between the 18F-FDG uptake levels and expression levels of HK2 and Glut1 in developed HCC showed a high 18F-FDG uptake in poorly differentiated HCCs that expressed high levels of HK2, in contrast to that in well-differentiated tumors. The progression of primary HCCs resembling human HCC in murine models was detected and monitored by 18F-FDG PET/CT. The correlation between tumor size and SUVmax was verified in the two HCC models. To the best of our knowledge, this is the first study to demonstrate that in vivo 18F-FDG uptake varies in HCCs according to differentiation grade in a preclinical study.
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea.
authors.forename: Ju Hui
authors.initials: JH
authors.lastname: Park
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea.
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea.
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea.
authors.forename: Tae Sup
authors.initials: TS
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea.
authors.forename: Kyeong Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea.
authors.forename: Ji Ae
authors.initials: JA
authors.lastname: Park
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea.
authors.forename: Yin Ohk
authors.initials: YO
authors.lastname: Ko
authors.affiliation: Animal Molecular Physiology Research Unit, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Sang-Soep
authors.initials: SS
authors.lastname: Nahm
authors.affiliation: Department of Nuclear Medicine, Gangnam Severance Hospital, Seoul 135-720, Republic of Korea.
authors.forename: Tae Joo
authors.initials: TJ
authors.lastname: Jeon
authors.affiliation: Department of Food Science and Biotechnology, Gachon University, Gyeonggi-do 461-701, Republic of Korea.
authors.forename: Young-Seo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, KIRAMS, Seoul 139-706, Republic of Korea.
authors.forename: Sang Moo
authors.initials: SM
authors.lastname: Lim
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000473:pathology*; D004052:Diethylnitrosamine / Q000633:toxicity*; D005260:Female; D019788:Fluorodeoxyglucose F18; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D051272:Glucose Transporter Type 1; D019275:Radiopharmaceuticals; C495678:Slc2a1 protein, mouse; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D019788:Fluorodeoxyglucose F18; D004052:Diethylnitrosamine; D006593:Hexokinase; C000598049:hexokinase 2, mouse