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Diffusion-weighted MRI and 18F-FDG PET correlation with immunity in early radiotherapy response in BNL hepatocellular carcinoma mouse model: timeline validation

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Imaging probes/biomarkers that are correlated with molecular or microenvironmental alterations in tumors have been used not only in diagnosing cancer but also in assessing the efficacy of cancer treatment. We evaluated the early response of hepatocellular carcinoma (HCC) to radiation treatment using T2-weighted magnetic resonance imaging (MRI), diffusion-weighted (DW) MRI, and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET).

Methods

Orthotopic HCC tumors were established in the right liver lobe of Balb/c mice. Mice were longitudinally scanned using T2-weighted/DW MRI and 18F-FDG PET 1 day before and on days 1, 3, 6, 9 and 13 after irradiation with 15 Gy to the right liver lobe to determine tumor size, apparent diffusion coefficient (ADC) value, and maximum standardized uptake value. Immunohistochemical (IHC) staining was performed to validate the tumor microenvironment.

Results

Irradiation markedly retarded tumor growth in the orthotopic HCC model and led to increaes in ADC values as early as on day 1 after irradiation. Irradiation also resulted in increases in 18F-FDG uptake on day 1 that were sustained until the end of the observation period. IHC staining revealed a decrease in the number of proliferative cells and a continuous macrophage influx into irradiated tumors, which dramatically altered the tumor microenvironment. Lastly, in vitro coculture of HCC cells and macrophages led to interaction between the cells and enhanced the cellular uptake of 18F-FDG.

Conclusion

ADC values and 18F-FDG uptake measured using DW MRI and 18F-FDG PET serve as potential biomarkers for early assessment of HCC tumor responses to radiation therapy.

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Acknowledgments

We thank the Radiation Biology Core Laboratory, Chang Gung Memorial Hospital, for their support in performing the radiation treatments and in immunohistochemistry imaging, and the Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, for their support in imaging.

Funding

This study was supported by Chang Gung Medical Foundation, Taiwan (grants CRRPG3E0014, CMRPG3B0313, and CMRPD1H0471) and the Ministry of Science and Technology (MOST 107-2314-B-182-068-MY2 to Fang-Hsin Chen, and MOST 106-2627-M-182A-002 to Tzu-Chen Yen).

Author information

Author notes

  1. Yi-Hsiu Chung and Ching-Fang Yu contributed equally to this work. Tzu-Chen Yen and Fang-Hsin Chen are corresponding authors.

Authors and Affiliations

  1. Center for Advanced Molecular Imaging and Translation (CAMIT), Chang Gung Memorial Hospital Linkou Branch, Taoyuan, 333, Taiwan

    Yi-Hsiu Chung, Shao-Chieh Chiu, Han Chiu, Shin-Ting Hsu & Tzu-Chen Yen

  2. Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan

    Ching-Fang Yu, Ching-Rong Wu, Ji-Hong Hong & Fang-Hsin Chen

  3. Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan

    Ching-Fang Yu, Ching-Rong Wu, Chung-Lin Yang, Ji-Hong Hong & Fang-Hsin Chen

  4. Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan City, Taiwan

    Chung-Lin Yang, Ji-Hong Hong & Fang-Hsin Chen

  5. Department of Nuclear Medicine, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, 333, Taiwan

    Tzu-Chen Yen

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  1. Yi-Hsiu Chung
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Correspondence to Tzu-Chen Yen or Fang-Hsin Chen.

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All procedures used in animal studies were in accordance with the ethical standards of our institution.

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Chung, YH., Yu, CF., Chiu, SC. et al. Diffusion-weighted MRI and 18F-FDG PET correlation with immunity in early radiotherapy response in BNL hepatocellular carcinoma mouse model: timeline validation. Eur J Nucl Med Mol Imaging 46, 1733–1744 (2019). https://doi.org/10.1007/s00259-019-04318-3

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