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Glucose-6-phosphatase Expression–Mediated [18F]FDG Efflux in Murine Inflammation and Cancer Models

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Abstract

Purpose

2-Deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) accumulation in inflammatory lesions can confound the diagnosis of cancer. In this study, we investigated [18F]FDG accumulation and efflux in relation to the genes and proteins involved in glucose metabolism in murine inflammation and cancer models.

Procedures

[18F]FDG accumulation and [18F]FDG efflux were measured in cancer cells (breast cancer, glioma, thyroid cancer, and hepatoma cells) and RAW 264.7 cells (macrophages) activated with lipopolysaccharide (LPS). The levels of mRNA expression were measured by real-time quantitative PCR (qPCR). The expression of glucose metabolism–related proteins was detected by western blotting. Dynamic [18F]FDG positron emission tomography-computed tomography (PET/CT) images were acquired for 2 h in tumor-bearing BALB/c nude mice and inflammatory mice induced by turpentine oil.

Results

[18F]FDG accumulation in MDA-MB-231 (breast cancer) increased with time, but that of HepG2 (hepatoma) reached a constant level after 120 min. [18F]FDG efflux in HepG2 was faster than that in MDA-MB-231. HepG2 strongly expressed glucose-6-phosphatase (G6Pase) compared with MDA-MB-231. [18F]FDG accumulation increased with time, and [18F]FDG efflux accelerated after the activation of RAW 264.7 cells. The expression levels of G6Pase, glucose transporter1 and glucose transporter3 (GLUT1 and GLUT3), and hexokinase II (HK II) increased after the activation of RAW 264.7 cells. [18F]FDG efflux in activated macrophages was faster than that in MDA-MB-231 cancer cells. MDA-MB-231 strongly expressed HK II protein compared with the activated RAW 264.7. In murine models, [18F]FDG accumulation in MDA-MB-231 cancer and inflammatory lesions increased with time, but that in HepG2 tumor increased until 20–30 min (SUVmeans ± SD (tumor/muscle), 3.0 ± 1.3) and then decreased (2.1 ± 0.9 at 110–120 min).

Conclusions

There was no difference in the pattern of [18F]FDG accumulation with time in MDA-MB-231 tumors and inflammatory lesions. We found that [18F]FDG efflux accelerated in activated macrophages reflecting increased G6Pase expression after activation and lower expression of HK II protein than that in MDA-MB-231 cancer cells.

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Acknowledgements

We thank Professor Jae Sung Lee and Seung Kwan Kang for the support of dynamic [18F]FDG PET imaging, and Young Ju Kim for technical assistant of mouse PET imaging.

Funding

This work was supported by internal research funds from the Seoul National University Cancer Research Institute (cri-15-4, cri-16-3, and cri-17-3) and grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare (grant numbers HI14C1072 and HI14C1277); the National Research Foundation of Korea (NRF) grant for the Global Core Research Center (GCRC) funded by the Korea government Ministry of Science, ICT and Future Planning (MSIP) (No. 2011-0030001) (2017-R1A2B4012813); and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2009-0093820).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea

    Mi Jeong Kim, Chul-Hee Lee, Youngeun Lee, Hyewon Youn, Keon Wook Kang, JoonHo Kwon, Gi Jeong Cheon & June-Key Chung

  2. Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Mi Jeong Kim, Hyewon Youn, Keon Wook Kang, Gi Jeong Cheon & June-Key Chung

  3. Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea

    Mi Jeong Kim, Hyewon Youn & June-Key Chung

  4. Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea

    Chul-Hee Lee, Keon Wook Kang & June-Key Chung

  5. Tumor Biology Program, Seoul National University College of Medicine, Seoul, South Korea

    Youngeun Lee & Gi Jeong Cheon

  6. Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul, South Korea

    Hyewon Youn

  7. Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea

    JoonHo Kwon

  8. Division of Nuclear Medicine, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Abass Alavi & Sean Carlin

  9. Department of Nuclear Medicine, National Cancer Center, Goyang, Republic of Korea

    June-Key Chung

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  1. Mi Jeong Kim
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Correspondence to Abass Alavi or June-Key Chung.

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Mi Jeong Kim, Chul-Hee Lee and Youngeun Lee contributed equally to this research.

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Kim, M.J., Lee, CH., Lee, Y. et al. Glucose-6-phosphatase Expression–Mediated [18F]FDG Efflux in Murine Inflammation and Cancer Models. Mol Imaging Biol 21, 917–925 (2019). https://doi.org/10.1007/s11307-019-01316-7

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