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An Innovation for Treating Orthotopic Pancreatic Cancer by Preoperative Screening and Imaging-Guided Surgery

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Abstract

Purpose

Pancreatic cancer is still associated with a poor outcome and low patient quality of life, which are mainly attributed to the late detection and requirement of distal pancreatectomy with extended resection of pancreatic tumors. Therefore, novel strategies for early screening and precise tumor resection are urgently needed. In this study, we evaluated the feasibility of a low-density lipoprotein receptor (LDLR)-targeted small-molecule contrast agent (peptide-22-Cy7) for early screening with photoacoustic tomography and near-infrared (NIR) imaging as guided surgical navigation to achieve precise resection.

Procedure

Normal pancreatic cells (HPDE6-C7) and cancer cells (PANC-1) were respectively used in the in vitro targeting evaluations. The ability of peptide-22-Cy7 for preoperative in vivo pancreatic tumor detection was investigated in a mouse orthotopic pancreatic cancer model (n = 10) using photoacoustic tomography; 18 tumor-bearing mice were further divided into three groups for different treatments. After intravenous injection of peptide-22-Cy7, surgical navigation was conducted through laparotomy. Histopathological analysis was used to further confirm the tumor area and the state of surgical margins.

Results

Flow cytometry demonstrated that peptide-22 is highly specific to pancreatic cancer cells, with a fluorescence intensity of approximately 87.3 %. Orthotopic pancreatic tumors with a size of 4 mm could be accurately detected by photoacoustic tomography. Surgical navigation effectively achieved R0 resection and minimized the range of resection, which led to increased body weight of the mice following surgery.

Conclusion

Overall, our newly developed targeted contrast agent facilitated the accurate positioning and resection of pancreatic tumors. Photoacoustic tomography and optical imaging-guided surgical navigation may be a novel direction for improving the survival, quality of life, and disease management of pancreatic cancer patients.

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Acknowledgements

The authors thank Tianpei Guan, Guanhua Lu, and Ting Ai for assistance with data collection.

Funding

This work was supported by the National Natural Science Foundation of China under Grant Nos. 81227901, 81627805, 61231004, 61671449, 81501540, and 81527805; National Key R&D Program of China Grant under No. 2017YFA0205200; The Science and Technology Plan Project of Guangzhou (No. 201604020144); Digital Theranostic Equipment Research Special Program of The “13th five-year” National Key Research Plan (No. 2016YFC0106500); and The United Fund of National Natural Science Foundation of China and Government of Guangdong Province (Grant No. U1401254).

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China

    Ziyu Han, Xiaoyuan Liang, Min Hu & Chihua Fang

  2. CAS Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China

    Ziyu Han, Wenting Shang, Hao Yan, Li Peng, Hongmei Jiang, Kun Wang & Jie Tian

  3. University of Chinese Academy of Sciences, Beijing, 100080, China

    Ziyu Han & Jie Tian

  4. Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, 510280, China

    Ziyu Han, Xiaoyuan Liang, Min Hu & Chihua Fang

  5. CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing, China

    Jie Tian

  6. CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Zhongguancun East Road #95, Haidian Dist, Beijing, 100190, China

    Jie Tian

Authors
  1. Ziyu Han
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  2. Wenting Shang
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  3. Xiaoyuan Liang
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  4. Hao Yan
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  5. Min Hu
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  8. Chihua Fang
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  9. Kun Wang
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Correspondence to Chihua Fang, Kun Wang or Jie Tian.

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Han, Z., Shang, W., Liang, X. et al. An Innovation for Treating Orthotopic Pancreatic Cancer by Preoperative Screening and Imaging-Guided Surgery. Mol Imaging Biol 21, 67–77 (2019). https://doi.org/10.1007/s11307-018-1209-8

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