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Monitoring Tumor Response After Histone Deacetylase Inhibitor Treatment Using 3′-Deoxy-3′-[18F]-fluorothymidine PET

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Abstract

Purpose

This study employed 3′-deoxy-3′-[18F]-fluorothymidine ([18F]FLT) microPET scanning to assess the treatment response of histone deacetylase inhibitors (HDACi), e.g., N1-hydroxy-N8-phenyloctanediamide (SAHA) and its iodinated derivative ISAHA, in a hepatoma mouse model.

Procedures

The in vitro cytotoxicity of HDACi in various hepatoma cell lines was determined by MTT assay and flow cytometry. ISAHA and SAHA were used to treat HepG2 hepatoma xenograft-bearing mice. The treatment responses were characterized in terms of tumor burden, microPET imaging, and immunohistochemical staining of tumor sections.

Results

ISAHA effectively inhibited HepG2 hepatoma cell survival and tumor growth. A significantly reduced tumor uptake during HDACi treatment was noticed in [18F]FLT microPET imaging, which was consistent with the findings in immunohistochemical staining.

Conclusions

ISAHA can suppress tumor cell proliferation both in vitro and in vivo. [18F]FLT PET is a promising modality for evaluating the in vivo therapeutic efficacy of HDACi at the early stage of treatment.

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Acknowledgments

The authors thank the financial support from National Science Council, Taiwan (NSC 101-2623-E-010-006-NU, NSC100-2623-E-010-003-NU, and NSC99-NU-E-010-003). The authors also appreciate the technical support provided by the Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan

    Pei-Chia Chan, Lin-Shan Chou, Chung-Hsien Ho, C. Allen Chang, Jeng-Jong Hwang & Hsin-Ell Wang

  2. Biophotonics & Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan

    Pei-Chia Chan, C. Allen Chang & Hsin-Ell Wang

  3. Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan

    Chun-Yi Wu

  4. National PET/Cyclotron Center, Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chi-Wei Chang & Ren-Shyan Liu

  5. Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

    Shih-Hwa Chiou

  6. Institute of Nuclear Energy Research, Atomic Energy Council, Tao-Yuan County, Taiwan

    Wuu-Jyh Lin

  7. Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan

    Fu-Du Chen

  8. Department of Nuclear Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Ren-Shyan Liu

  9. Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan

    Ren-Shyan Liu

Authors
  1. Pei-Chia Chan
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  2. Chun-Yi Wu
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  3. Lin-Shan Chou
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  4. Chung-Hsien Ho
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  9. C. Allen Chang
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  10. Jeng-Jong Hwang
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  11. Ren-Shyan Liu
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Corresponding authors

Correspondence to Ren-Shyan Liu or Hsin-Ell Wang.

Additional information

Pei-Chia Chan and Chun-Yi Wu contribute equally to this work.

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Chan, PC., Wu, CY., Chou, LS. et al. Monitoring Tumor Response After Histone Deacetylase Inhibitor Treatment Using 3′-Deoxy-3′-[18F]-fluorothymidine PET. Mol Imaging Biol 17, 394–402 (2015). https://doi.org/10.1007/s11307-014-0774-8

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  • DOI: https://doi.org/10.1007/s11307-014-0774-8

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