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Adenine Nucleotide Translocase 2 as an Enzyme Related to [18F] FDG Accumulation in Various Cancers

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Abstract

Purpose

Although glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) are known as major proteins involved in the molecular mechanisms for accumulating 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in cancer cells, sometimes, [18F] FDG accumulation cannot be explained by the expression of these two proteins. We investigated the involvement of adenine nucleotide translocase 2 (ANT2), which catalyzes ADP/ATP exchange at the mitochondrial inner membrane, in [18F] FDG accumulation.

Procedures

ANT2 expression was evaluated in various cancer cell lines and human cancer tissues (microarrays) using western blot and immunohistochemical (IHC) staining, respectively. The expression levels of ANT2 were compared to [18F] FDG accumulation and pathologic findings, including differentiation grade. Additionally, we modulated ANT2 expression levels using ANT2 siRNA and an ANT2 expression vector in cancer cells and murine xenografted tumors.

Results

[18F] FDG accumulation correlated with ANT2 expression in various cancer cell lines; this was not explained by GLUT1 and/or HK2 expression. At both the cell and tissue levels, ANT2 expression was high in less-differentiated or more malignant type of cancers. [18F] FDG accumulation changed according to the modulation of the ANT2 expression level.

Conclusion

In various cancer cells and tissues, the expression levels of ANT2 explained [18F] FDG accumulation better than those of GLUT1 and HK2. ANT2 can be used as a marker of dedifferentiated pathology and aggressiveness of cancer.

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Funding

This work was supported by grants from the National Research Foundation, Ministry of Science and ICT (2011-0030001 for J-K.C. and H.Y., 2017-R1A2B4012813 for H.Y.), and the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C1072 for K.W.K, G.J.C. and H.Y., HI15C2971 for H.Y.).

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Authors and Affiliations

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

    Chul-Hee Lee, Mi Jeong Kim, Hwan Hee Lee, Jin Chul Paeng, So Won Oh, Gi Jeong Cheon, Keon Wook Kang, Hyewon Youn & June-Key Chung

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

    Chul-Hee Lee & June-Key Chung

  3. Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

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

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

    Chul-Hee Lee, Mi Jeong Kim, Hyewon Youn & June-Key Chung

  5. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea

    Young Joo Park

  6. Department of Nuclear medicine, Seoul National University Boramae Medical Center, Seoul, South Korea

    So Won Oh

  7. Department of Surgery, Seoul National University Boramae Medical Center, Seoul, South Korea

    Young Jun Chai

  8. Department of Pathology, Seoul National University Boramae Medical Center, Seoul, South Korea

    Young A. Kim

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

    Hyewon Youn

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  1. Chul-Hee Lee
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  2. Mi Jeong Kim
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  3. Hwan Hee Lee
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  8. Young A. Kim
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  12. June-Key Chung
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Corresponding authors

Correspondence to Hyewon Youn or June-Key Chung.

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The authors declare that they have no conflict of interest.

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Lee, CH., Kim, M.J., Lee, H.H. et al. Adenine Nucleotide Translocase 2 as an Enzyme Related to [18F] FDG Accumulation in Various Cancers. Mol Imaging Biol 21, 722–730 (2019). https://doi.org/10.1007/s11307-018-1268-x

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