J Gastric Cancer.
2021 Jun;21(2):191-202. 10.5230/jgc.2021.21.e18.
Evaluation of Near-infrared Fluorescence-conjugated Peptides for Visualization of Human Epidermal Receptor 2-overexpressed Gastric Cancer
- Jeong K
1 - Kong SH2,3
- Bae SW1
- Park CR1,4,5
- Berlth F6
- Shin JH7
- Lee YS1,7
- Youn H4,5
- Koo E1
- Suh YS2,3,8
- Park DJ1,2,3
- Lee HJ1,2,3
- Yang HK1,2,3
- Affiliations
-
- 1Cancer Research Institute, Seoul National University, Seoul, Korea
- 2Department of Surgery, Seoul National University Hospital, Seoul, Korea
- 3Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- 4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
- 5Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea
- 6Department of General, Visceral and Transplant Surgery, University of Mainz, Mainz, Germany
- 7Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine Seoul, Korea
- 8Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- KMID: 2526316
- DOI: http://doi.org/10.5230/jgc.2021.21.e18
Abstract
- 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. AffibodyIRDye800CW 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. Affibodybased NIR probes may require modifications to enhance mobilization to the tumor site.
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