Glucose-6-phosphatase Expression–Mediated [18F]FDG Efflux in Murine Inflammation and Cancer Models
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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.
[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.
[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).
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.
Key words2-Deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) Positron emission tomography (PET) Inflammation Cancer Glucose-6-phosphatase (G6Pase)
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.
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).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 5.Smith TA (1999) Facilitative glucose transporter expression in human cancer tissue. Br J Biomed Sci 56:285–292Google Scholar
- 8.Ishimori T, Saga T, Mamede M, Kobayashi H, Higashi T, Nakamoto Y, Sato N, Konishi J (2002) Increased 18F-FDG uptake in a model of inflammation: concanavalin A-mediated lymphocyte activation. J Nucl Med 43:658–663Google Scholar
- 12.Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, Mozley PD, Rossman MD, Albelda SM, Alavi A (2001) Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med 42:1412–1417Google Scholar
- 17.Yamada S, Kubota K, Kubota R et al (1995) High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med 36:1301–1306Google Scholar
- 22.Airley R, Loncaster J, Davidson S, Bromley M, Roberts S, Patterson A, Hunter R, Stratford I, West C (2001) Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix. Clin Cancer Res 7:928–934Google Scholar
- 25.Hustinx R, Smith RJ, Benard F, Rosenthal DI, Machtay M, Farber LA, Alavi A (1999) Dual time point fluorine-18 fluorodeoxyglucose positron emission tomography: a potential method to differentiate malignancy from inflammation and normal tissue in the head and neck. Eur J Nucl Med 26:1345–1348CrossRefGoogle Scholar
- 29.Matthies A, Hickeson M, Cuchiara A, Alavi A (2002) Dual time point 18F-FDG PET for the evaluation of pulmonary nodules. J Nucl Med 43:871–875Google Scholar