Evaluation of diethylnitrosamine- or hepatitis B virus X gene-induced hepatocellular carcinoma with 18F-FDG PET/CT: A preclinical study

Park,Ju  Hui; Kang,Joo  Hyun; Lee,Yong  Jin; Kim,Kwang  Il; Lee,Tae  Sup; Kim,Kyeong  Min; Park,Ji  Ae; Ko,Yin  Ohk; Yu,Dae-Yeul; Nahm,Sang-Soep; Jeon,Tae  Joo; Park,Young-Seo; Lim,Sang  Moo

doi:10.3892/or.2014.3575

Evaluation of diethylnitrosamine- or hepatitis B virus X gene-induced hepatocellular carcinoma with 18F-FDG PET/CT: A preclinical study

Authors:
- Ju Hui Park
- Joo Hyun Kang
- Yong Jin Lee
- Kwang Il Kim
- Tae Sup Lee
- Kyeong Min Kim
- Ji Ae Park
- Yin Ohk Ko
- Dae-Yeul Yu
- Sang-Soep Nahm
- Tae Joo Jeon
- Young-Seo Park
- Sang Moo Lim
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Affiliations: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea, Animal Molecular Physiology Research Unit, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea, Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea, Department of Nuclear Medicine, Gangnam Severance Hospital, Seoul 135-720, Republic of Korea, Department of Food Science and Biotechnology, Gachon University, Gyeonggi-do 461-701, Republic of Korea, Department of Nuclear Medicine, KIRAMS, Seoul 139-706, Republic of Korea
Published online on: October 30, 2014 https://doi.org/10.3892/or.2014.3575
Pages: 347-353

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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.

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