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Mol Imaging Biol. 2016 Dec;18(6):820-829.

A Clinical Wide-Field Fluorescence Endoscopic Device for Molecular Imaging Demonstrating Cathepsin Protease Activity in Colon Cancer.

Sensarn S1,2,3, Zavaleta CL1,3, Segal E4, Rogalla S2, Lee W1,5, Gambhir SS1,3,6,7, Bogyo M4, Contag CH8,9,10,11,12.

Author information

1
Department of Radiology, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA.
2
Department of Pediatrics, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA.
3
Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, 94305, USA.
4
Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
5
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
6
Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
7
Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
8
Department of Radiology, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA. ccontag@stanford.edu.
9
Department of Pediatrics, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA. ccontag@stanford.edu.
10
Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, 94305, USA. ccontag@stanford.edu.
11
Department of Microbiology & Immunology, Stanford University, Stanford, CA, 94305, USA. ccontag@stanford.edu.
12
Stanford University, 318 Campus Drive, Stanford, CA, 94305-5427, USA. ccontag@stanford.edu.

Abstract

PURPOSE:

Early and effective detection of cancers of the gastrointestinal tract will require novel molecular probes and advances in instrumentation that can reveal functional changes in dysplastic and malignant tissues. Here, we describe adaptation of a wide-field clinical fiberscope to perform wide-field fluorescence imaging while preserving its white-light capability for the purpose of providing wide-field fluorescence imaging capability to point-of-care microscopes.

PROCEDURES:

We developed and used a fluorescent fiberscope to detect signals from a quenched probe, BMV109, that becomes fluorescent when cleaved by, and covalently bound to, active cathepsin proteases. Cathepsins are expressed in inflammation- and tumor-associated macrophages as well as directly from tumor cells and are a promising target for cancer imaging. The fiberscope has a 1-mm outer diameter enabling validation via endoscopic exams in mice, and therefore we evaluated topically applied BMV109 for the ability to detect colon polyps in an azoxymethane-induced colon tumor model in mice.

RESULTS:

This wide-field endoscopic imaging device revealed consistent and clear fluorescence signals from BMV109 that specifically localized to the polypoid regions as opposed to the normal adjacent colon tissue (p < 0.004) in the murine colon carcinoma model.

CONCLUSIONS:

The sensitivity of detection of BMV109 with the fluorescence fiberscope suggested utility of these tools for early detection at hard-to-reach sites. The fiberscope was designed to be used in conjunction with miniature, endoscope-compatible fluorescence microscopes for dual wide-field and microscopic cancer detection.

KEYWORDS:

Biomedical optics; Endoscopy; Fiber optics; Fluorescence; Imaging systems; Medical imaging; Optical imaging; Optical probes

PMID:
27154508
PMCID:
PMC5564400
DOI:
10.1007/s11307-016-0956-7
[Indexed for MEDLINE]
Free PMC Article

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