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Dynamic Change of Amide Proton Transfer Imaging in Irradiated Nasopharyngeal Carcinoma and Related Histopathological Mechanism

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Abstract

Objective

To investigate the dynamic change of amide proton transfer (APT) imaging before and after irradiation in nasopharyngeal carcinoma (NPC) and the underlying histopathological mechanism.

Materials and Methods

Tumor-bearing BALB/C nude mouse models were established and randomly divided into three groups: high-dose group (20 Gy/2 fractions), low-dose group (10 Gy/2 fractions), and control group (0 Gy). MRI scanning was performed before irradiation and 3rd, 6th, and 9th day post-irradiation. Scanning sequence included T1 weighted, T2 weighted, and APT. HE staining and TUNEL immunofluorescence detection were performed to detect necrosis and apoptosis.

Results

After high-dose irradiation, the mean tumor APT values decreased significantly on the 3rd day and 6th day (from 3.83 before radiotherapy to 2.41%, P < 0.001, 3rd day; from 2.41 to 1.80%, P = 0.001, 6th day). For low-dose irradiation, the mean tumor APT values decreased slightly on the 3rd day and 6th day (from 3.52 to 3.13%, P = 0.109, 3rd day; from 3.13 to 3.05%, P = 0.64, 6th day). The mean APT values of nonirradiated tumor changed slightly. In contrast, the average volume of high-dose irradiated tumors did not decrease obviously until the 9th day post-irradiation (from 290 before radiotherapy to 208 mm3 on the 9th day). The low-dose irradiated tumors showed slow growth, and the nonirradiated tumors showed rapid growth. Subsequent HE staining and TUNEL staining showed obvious necrosis characteristics and higher proportion of positive apoptotic cell nucleus in high-dose irradiated tumors, but not nonirradiated tumors.

Conclusion

The APT signal intensity decreased after irradiation, which is earlier than the change of tumor volume. What is more, the decrease of APT signal intensity is more significant in high-dose group. Histological analysis showed obvious apoptosis and necrosis histological characteristic in irradiated tumor, which may explain the decrease of APT signal intensity. These results indicate that APT imaging has the potential to serve as a reliable biomarker for response assessment in NPC.

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Acknowledgements

The authors thank Professor Jinyuan Zhou (John Hopkins University) and Professor Yi Zhang (Zhejiang University) for technical assistance with APT imaging. We also thank engineer Weibo Chen (Philips Healthcare) for technical assistance with MRI. We thank engineer Xuefeng Zhang (Qilu hospital) and Jianzhen Wang (Qilu hospital) for animal irradiation.

Funding

This study was funded by the Special Fund for Taishan Scholar Project (Grant No. ts20190973) and the National Natural Science Foundation of China (Grant No. 81773228).

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Authors and Affiliations

  1. Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China

    Qingxu Song, Pengxiang Chen, Jianbo Wang, Bingxu Tan, Hong Liu & Yufeng Cheng

  2. Department of MR, Shandong Medical Imaging Research Institute, Jinan, Shandong, People’s Republic of China

    Xin Chen & Cong Sun

Authors
  1. Qingxu Song
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  2. Pengxiang Chen
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  3. Xin Chen
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  4. Cong Sun
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  5. Jianbo Wang
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  6. Bingxu Tan
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  7. Hong Liu
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  8. Yufeng Cheng
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Qingxu Song, Pengxiang Chen, Cong Sun, and Xin Chen. The first draft of the manuscript was written by Qingxu Song, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yufeng Cheng.

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Song, Q., Chen, P., Chen, X. et al. Dynamic Change of Amide Proton Transfer Imaging in Irradiated Nasopharyngeal Carcinoma and Related Histopathological Mechanism. Mol Imaging Biol 23, 846–853 (2021). https://doi.org/10.1007/s11307-021-01607-y

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  • DOI: https://doi.org/10.1007/s11307-021-01607-y

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