Theranostics 2012; 2(2):227-234. doi:10.7150/thno.4088

Research Paper

Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy

Peiman Habibollahi1, Jose-Luiz Figueiredo2, Pedram Heidari1, Austin M Dulak3, Yu Imamura4, Adam J. Bass3, Shuji Ogino3, 4, Andrew T Chan5, Umar Mahmood1✉

1. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital,
2. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital,
3. Department of Medical Oncology, Dana-Farber Cancer Institute,
4. Department of Pathology, Brigham and Women's Hospital,
5. Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Habibollahi P, Figueiredo JL, Heidari P, Dulak AM, Imamura Y, Bass AJ, Ogino S, Chan AT, Mahmood U. Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy. Theranostics 2012; 2(2):227-234. doi:10.7150/thno.4088. Available from

File import instruction


Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64±0.14 and 4.50±0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88±0.04 and 0.81±0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions.

Keywords: Esophageal Adenocarcinoma, Cathepsin B, Prosense750, Near Infrared Imaging.