Journal of Gastric Cancer

  • 제21권2호
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  • Pages.191-202
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  • 2021
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  • 2093-582X(pISSN)
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  • 2093-5641(eISSN)
대한위암학회 (The Korean Gastric Cancer Association)
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Evaluation of Near-infrared Fluorescence-conjugated Peptides for Visualization of Human Epidermal Receptor 2-overexpressed Gastric Cancer

  • Jeong, Kyoungyun (Cancer Research Institute, Seoul National University) ;
  • Kong, Seong-Ho (Department of Surgery, Seoul National University Hospitall) ;
  • Bae, Seong-Woo (Cancer Research Institute, Seoul National University) ;
  • Park, Cho Rong (Cancer Research Institute, Seoul National University) ;
  • Berlth, Felix (Department of General, Visceral and Transplant Surgery, University of Mainz) ;
  • Shin, Jae Hwan (Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine) ;
  • Lee, Yun-Sang (Cancer Research Institute, Seoul National University) ;
  • Youn, Hyewon (Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Koo, Eunhee (Cancer Research Institute, Seoul National University) ;
  • Suh, Yun-Suhk (Department of Surgery, Seoul National University Hospitall) ;
  • Park, Do Joong (Cancer Research Institute, Seoul National University) ;
  • Lee, Hyuk-Joon (Cancer Research Institute, Seoul National University) ;
  • Yang, Han-Kwang (Cancer Research Institute, Seoul National University)
  • 투고 : 2021.04.29
  • 심사 : 2021.06.17
  • 발행 : 2021.06.30
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초록

Purpose: A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Materials and Methods: An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6-8 weeks old) mice. After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart). Results: Trastuzumab-IRDye800CW exhibited high affinity for HER2 (KD=2.093(3) pM). Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. Affibody-IRDye800CW also exhibited high affinity for HER2 (KD=4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance. Conclusions: Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2-3 days before surgery to obtain high HER2-specific signal and contrast. Affibody-based NIR probes may require modifications to enhance mobilization to the tumor site.

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과제정보

We would like to thank Leena Lim and Editage (www.editage.co.kr) for English language editing.

참고문헌

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