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

Habibollahi, Peiman; Figueiredo, José-Luiz; Heidari, Pedram; Dulak, Austin; Imamura, Yu; Bass, Adam J.; Ogino, Shuji; Chan, Andrew T.; Mahmood, Umar

doi:10.7150/thno.4088

Cited by 46 publications

(37 citation statements)

References 18 publications

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“…Upon CB cleavage of the substrate sequence, the agent becomes highly fluorescent in target areas. This architecture offers higher target specific signals with reduced background compared to previous similar probe such as proSense 680 and proSense 750 [23], [24]. ProSense 680 and proSense 750 are broad cathepsins activatable fluorescent imaging probes which are sensitive to cathepsin B/H/L/S instead of single CB.…”

Section: Discussionmentioning

confidence: 99%

Detection of Esophageal Squamous Cell Carcinoma by Cathepsin B Activity in Nude Mice

Zhe

et al. 2014

PLoS ONE

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Background and ObjectiveDespite great progress in treatment, the prognosis for patients with esophageal squamous cell carcinoma (ESCC) remains poor, highlighting the importance of early detection. Although upper endoscopy can be used for the screening of esophagus, it has limited sensitivity for early stage disease. Thus, development of new diagnosis approach to improve diagnostic capabilities for early detection of ESCC is an important need. The aim of this study was to assess the feasibility of using cathepsin B (CB) as a novel imaging target for the detection of human ESCC by near-infrared optical imaging in nude mice.MethodsInitially, we examined specimens from normal human esophageal tissue, intraepithelial neoplasia lesions, tumor in situ, ESCC and two cell lines including one human ESCC cell line (Eca-109) and one normal human esophageal epithelial cell line (HET-1A) for CB expression by immunohistochemistry and western blot, respectively. Next, the ability of a novel CB activatable near-infrared fluorescence (NIRF) probe detecting CB activity presented in Eca-109 cells was confirmed by immunocytochemistry. We also performed in vivo imaging of tumor bearing mice injected with the CB probe and ex vivo imaging of resected tumor xenografts and visceral organs using a living imaging system. Finally, the sources of fluorescence signals in tumor tissue and CB expression in visceral organs were identified by histology.ResultsCB was absent in normal human esophageal mucosa, but it was overexpressed in ESCC and its precursor lesions. The novel probe for CB activity specifically detected ESCC xenografts in vivo and in vitro.ConclusionsCB was highly upregulated in human ESCC and its precursor lesions. The elevated CB expression in ESCC allowed in vivo and in vitro detection of ESCC xenografts in nude mice. Our results support the usefulness of CB activity as a potential imaging target for the detection of human ESCC.

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Section: Discussionmentioning

confidence: 99%

Detection of Esophageal Squamous Cell Carcinoma by Cathepsin B Activity in Nude Mice

Zhe

et al. 2014

PLoS ONE

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“…Habibollahi et al used white-light upper endoscopy combined with near-infrared imaging to detect cathepsin B and thereby screen for esophageal adenocarcinoma [62]. The results indicate that cathepsin B appears to have huge potential for clinical applications.…”

Section: Esophageal Cancermentioning

confidence: 99%

Cathepsins in digestive cancers

et al. 2017

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Cathepsins are lysosomal peptidases belonging to the papain family, and based on their catalytic sites, these enzymes can be divided into serine, cysteine and aspartic proteases. The studies conducted to date have identified, 15 types of cathepsins that are widely distributed in intracellular and extracellular spaces. These proteases participate in various pathological activities, including the occurrence and development of human cancers. Several recent studies suggest that cathepsins, particularly cathepsins B, D, E and L, contribute to digestive tumorigenesis. Cathepsins were found to promote the development of most digestive cancers except liver cancer, in which they might have the opposite effects. Due to their important roles in digestive tumors, cathepsins might be therapeutic targets for the treatment of digestive cancers.

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“…One drawback to these agents, however, was the relatively long incubation period needed to convert the probe to its activated state. By changing the dye to ProSense ® 750 (Perkin Elmer Inc., MA, USA), this incubation time could be reduced with better fluorescence output [74,75].…”

Section: Enzymatically Activatable Probesmentioning

confidence: 99%

Endoscopic Molecular Imaging of Cancer

2013

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White light endoscopy has proven to be a very powerful tool in oncology. There is still, however, a need for better endoscopic techniques to overcome the current limitations of white light optics. New technologies that allow higher sensitivity, improved microanatomy and molecular characterization have been available for in vitro microscopy and are now being translated into in vivo endoscopy. Endoscopic molecular imaging is still in its infancy but holds the promise for enhancing sensitivity for early lesions, thus allowing earlier diagnosis and enabling early image-guided endoscopic intervention. A key feature of endoscopic molecular imaging is its increased sensitivity and specificity, which will be illustrated in this article, as well as describing perspectives on its future use in oncologic surgery.

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

Cited by 46 publications

References 18 publications

Detection of Esophageal Squamous Cell Carcinoma by Cathepsin B Activity in Nude Mice

Detection of Esophageal Squamous Cell Carcinoma by Cathepsin B Activity in Nude Mice

Cathepsins in digestive cancers

Endoscopic Molecular Imaging of Cancer

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