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Targeting visualization of malignant tumor based on the alteration of DWI signal generated by hTERT promoter–driven AQP1 overexpression

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

Abstract

Purpose

To specifically diagnose malignant tumors in DWI using the human telomerase reverse transcriptase (hTERT) promoter–driven AQP1 expression.

Methods

The human telomerase reverse transcriptase (hTERT) promoter–driven AQP1 gene overexpression lentivirus system (hTERT-AQP1) and cytomegalovirus (CMV) promoter–driven AQP1 gene overexpression lentivirus system (CMV-AQP1) were prepared, and transduced into telomerase-positive and -negative cells. The AQP1 expression and DWI signal intensity (SI) change in transduced cells were analyzed. Balb/C nude mice subcutaneous xenograft models derived from lentivirus-transduced telomerase-positive and -negative cells were used to evaluate AQP1 expression and DWI SI change in vivo. We further established another group of subcutaneous xenograft model using pristine telomerase-positive and -negative cells, followed by injecting the lentiviral vectors intratumorally or intravenously, to determine the malignant tumor-targeted imaging of hTERT-AQP1.

Results

The hTERT-AQP1 and CMV-AQP1 were successfully prepared. After transduction, hTERT-AQP1 could induce the specific overexpression of AQP1 in telomerase-positive cells. Compared with untransduced cells, all CMV-AQP1-pretransduced cells and hTERT-AQP1-pretransduced telomerase-positive cells showed decreased SI and increased apparent diffusion coefficient (ADC) in DWI, while hTERT-AQP1-pretransduced telomerase-negative cells showed no obvious SI and ADC change. Correspondingly, hTERT-AQP1-transduced telomerase-positive tumors and CMV-AQP1-transduced telomerase-positive and -negative tumors showed decreased DWI SI and increased ADC, while hTERT-AQP1-transduced telomerase-negative tumor had no SI and ADC changes. After intratumoral or intravenous injection, CMV-AQP1 could upregulate AQP1 expression and induce DWI SI and ADC alteration in both telomerase-positive and -negative tumors, while hTERT-AQP1 worked in telomerase-positive tumors specifically.

Conclusion

Cancers can be specifically visualized based on the DWI signal alteration which triggered by hTERT-AQP1 lentivirus system that combined AQP1 gene and hTERT promoter.

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Data availability

Data and materials are available for research purposes from the corresponding authors upon reasonable request.

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Funding

This research was supported by Natural Science Foundation of Chongqing, China (cstc2018jcyjAX0321 and cstc2021jcyj-msxmX1093), Natural Science Foundation of Army Medical University (No. 2019R059 and 2019R020), and Talents project of ChongQing, China (Dong Zhang).

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Authors and Affiliations

  1. Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China

    Liang Zhang, Mingfu Gong, Sheng Lei, Chun Cui, Yun Liu, Shilin Xiao, Xun Kang, Tao Sun, Zhongsheng Xu, Chunyu Zhou, Si Zhang & Dong Zhang

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  1. Liang Zhang
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  2. Mingfu Gong
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Contributions

LZ, MG, and DZ designed the experiments; LZ and MG prepared the lentivirus; LZ and MG analyzed AQP1 expression; LZ, SL, CC, and SZ conducted the MRI experiments, LZ and ZX established the tumor models; LZ, MG, YL, SX, XK, and TS performed statistical and MRI analysis; LZ, MG, SL, CZ, and DZ interpreted data and wrote, reviewed, revised manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Mingfu Gong or Dong Zhang.

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All experiments involving animals were performed following the National Institutes of Health guidelines on the use of animals in research and were approved by the Laboratory Animal Welfare and Ethics Committee of the Army Medical University, Chongqing, China.

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The authors declare no competing interests.

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Zhang, L., Gong, M., Lei, S. et al. Targeting visualization of malignant tumor based on the alteration of DWI signal generated by hTERT promoter–driven AQP1 overexpression. Eur J Nucl Med Mol Imaging 49, 2310–2322 (2022). https://doi.org/10.1007/s00259-022-05684-1

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