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ACS Nano. 2019 Feb 26;13(2):1354-1364. doi: 10.1021/acsnano.8b06808. Epub 2019 Feb 4.

Detection of Premalignant Gastrointestinal Lesions Using Surface-Enhanced Resonance Raman Scattering-Nanoparticle Endoscopy.

Author information

1
Department of Radiology , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States.
2
Department of Pediatrics , Stanford University , Stanford , California 94305 , United States.
3
Department of Radiology , Stanford University , Stanford , California 94305 , United States.
4
Urology Service, Department of Surgery, Sidney Kimmel Center for Prostate and Urologic Cancers , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States.
5
Department of Neurosurgery , University Hospital Cologne , Cologne 50937 , Germany.
6
Department of Medicine , Columbia University , New York , New York 10032 , United States.
7
Research Engineering Lab , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States.
8
Laser Biomedical Research Center, G. R. Harrison Spectroscopy Laboratory , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
9
Tri-Institutional Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center , The Rockefeller University, and Weill Cornell Medical College , New York , New York 10065 , United States.
10
Cancer Biology and Genetics Program , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States.
11
Department of Pathology , Stanford University , Stanford , California 94305 , United States.
12
Department of Bioengineering, Department of Materials Science & Engineering, Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection , Stanford University , Stanford , California 94305 , United States.
13
Department of Microbiology and Immunology , Stanford University , Stanford , California 94305 , United States.
14
Institute of Quantitative Health Science and Engineering, Department of Biomedical Engineering, and Department of Microbiology and Molecular Genetics , Michigan State University , East Lansing , Michigan 48824 , United States.
15
Center for Molecular Imaging and Nanotechnology (CMINT) , Memorial Sloan Kettering Cancer Center , 1275 York Avenue , New York , New York 10065 , United States.
16
Department of Molecular Pharmacology , Memorial Sloan Kettering Cancer Center , 1275 York Avenue , New York , New York 10065 , United States.
17
Department of Imaging , Dana-Farber Cancer Institute & Harvard Medical School , 450 Brookline Avenue , Boston , Massachusetts 02215 , United States.

Abstract

Cancers of the gastrointestinal (GI) tract are among the most frequent and most lethal cancers worldwide. An important reason for this high mortality is that early disease is typically asymptomatic, and patients often present with advanced, incurable disease. Even in high-risk patients who routinely undergo endoscopic screening, lesions can be missed due to their small size or subtle appearance. Thus, current imaging approaches lack the sensitivity and specificity to accurately detect incipient GI tract cancers. Here we report our finding that a single dose of a high-sensitivity surface-enhanced resonance Raman scattering nanoparticle (SERRS-NP) enables reliable detection of precancerous GI lesions in animal models that closely mimic disease development in humans. Some of these animal models have not been used previously to evaluate imaging probes for early cancer detection. The studies were performed using a commercial Raman imaging system, a newly developed mouse Raman endoscope, and finally a clinically applicable Raman endoscope for larger animal studies. We show that this SERRS-NP-based approach enables robust detection of small, premalignant lesions in animal models that faithfully recapitulate human esophageal, gastric, and colorectal tumorigenesis. This method holds promise for much earlier detection of GI cancers than currently possible and could lead therefore to marked reduction of morbidity and mortality of these tumor types.

KEYWORDS:

Raman; cancer; early detection; endoscopy; nanoparticle; preclinical

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