Wide-field multiplexed imaging of EGFR-targeted cancers using topical application of NIR SERS nanoprobes.

AIM As the possibilities of molecular imaging in personalized medicine evolve rapidly, the optical advantages of extremely narrow and intense spectral bands makes surface-enhanced Raman scattering (SERS) an appealing candidate for multiplexed recognition of targeted biomarkers over other optical imaging modalities. MATERIALS & METHODS In this proof-of-concept study, we report wide-field Raman detection of lung cancer using multimodal SERS nanoprobes specific to the EGF receptor family, both in vitro and in vivo. RESULTS For the first time, we demonstrate wide-field multiplexed Raman imaging for cancer detection in vivo after topical application of a 'cocktail' of SERS nanoprobes. CONCLUSION This advancement represents a key step towards sensitive wide-field Raman endoscopic imaging of multiple biomarkers for early and accurate diagnosis of EGF receptor-expressing tumors of different internal organs.

[1]  A. Saftoiu,et al.  Autofluorescence imaging and magnification endoscopy. , 2011, World journal of gastroenterology.

[2]  M. Natan,et al.  Glass-Coated, Analyte-Tagged Nanoparticles: A New Tagging System Based on Detection with Surface-Enhanced Raman Scattering , 2003 .

[3]  M. Neurath,et al.  Methylene Blue-Aided In Vivo Staining of Central Airways during Flexible Bronchoscopy , 2012, TheScientificWorldJournal.

[4]  Brian C. Wilson,et al.  Development of a widefield SERS imaging endoscope , 2012, Photonics West - Biomedical Optics.

[5]  Jesse V Jokerst,et al.  Gold nanorods for ovarian cancer detection with photoacoustic imaging and resection guidance via Raman imaging in living mice. , 2012, ACS nano.

[6]  Michal Wojcik,et al.  Supporting Information for High-Throughput Graphene Imaging on Arbitrary Substrates with Widefield Raman Spectroscopy , 2011 .

[7]  G. Scagliotti,et al.  Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. , 2003, Lung cancer.

[8]  Christopher H Contag,et al.  High-sensitivity, real-time, ratiometric imaging of surface-enhanced Raman scattering nanoparticles with a clinically translatable Raman endoscope device , 2013, Journal of biomedical optics.

[9]  Joel Greshock,et al.  Genome-wide DNA copy number predictors of lapatinib sensitivity in tumor-derived cell lines , 2008, Molecular Cancer Therapeutics.

[10]  A. Italiano,et al.  Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[11]  Igor L. Medintz,et al.  Potential clinical applications of quantum dots , 2008, International journal of nanomedicine.

[12]  T. M. Herne,et al.  The design and implementation of a high‐fidelity Raman imaging microscope , 1996, Journal of microscopy.

[13]  Gorka Bastarrika,et al.  Molecular Profiling of Computed Tomography Screen-Detected Lung Nodules Shows Multiple Malignant Features , 2006, Cancer Epidemiology Biomarkers & Prevention.

[14]  U. S. Dinish,et al.  Multiplex targeted in vivo cancer detection using sensitive near-infrared SERS nanotags , 2012 .

[15]  Jesse V Jokerst,et al.  Affibody-functionalized gold-silica nanoparticles for Raman molecular imaging of the epidermal growth factor receptor. , 2011, Small.

[16]  Myung-Gyu Choi,et al.  Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms. , 2012, World journal of gastrointestinal endoscopy.

[17]  Sebastian Schlücker,et al.  SERS microscopy: nanoparticle probes and biomedical applications. , 2009, Chemphyschem : a European journal of chemical physics and physical chemistry.

[18]  G. Fontanini,et al.  Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa). , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  Sebastian Schlücker,et al.  Raman microspectroscopy: a comparison of point, line, and wide-field imaging methodologies. , 2003, Analytical chemistry.

[20]  Armando Santoro,et al.  Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. , 2004, The New England journal of medicine.

[21]  R. Kiesslich,et al.  Chromoendoscopy with Indigocarmine Improves the Detection of Adenomatous and Nonadenomatous Lesions in the Colon , 2001, Endoscopy.

[22]  Timothy D. Soper,et al.  Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide‐field, full‐color imaging , 2010, Journal of biophotonics.

[23]  Brian C Wilson,et al.  Filter-based method for background removal in high-sensitivity wide-field-surface-enhanced Raman scattering imaging in vivo. , 2012, Journal of biomedical optics.

[24]  Wilfried van Sark,et al.  Photooxidation and Photobleaching of Single CdSe/ZnS Quantum Dots Probed by Room-Temperature Time-Resolved Spectroscopy , 2001 .

[25]  Sharmila Anandasabapathy,et al.  Optical molecular imaging for detection of Barrett's-associated neoplasia. , 2011, World journal of gastroenterology.

[26]  Sanjiv S. Gambhir,et al.  Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy , 2009, Proceedings of the National Academy of Sciences.

[27]  M. Wong,et al.  The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer , 2006, European Respiratory Journal.

[28]  T. Fujii,et al.  Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK , 2000, The Lancet.

[29]  Irene Manrique,et al.  Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model , 2010, BMC Cancer.

[30]  C. Dooms,et al.  Diagnostic bronchoscopy: state of the art , 2010, European Respiratory Review.

[31]  S. Gambhir,et al.  Noninvasive molecular imaging of small living subjects using Raman spectroscopy , 2008, Proceedings of the National Academy of Sciences.

[32]  Stuart A. Taylor,et al.  Nonlaxative PET/CT Colonography: Feasibility, Acceptability, and Pilot Performance in Patients at Higher Risk of Colonic Neoplasia , 2010, Journal of Nuclear Medicine.

[33]  Brian C Wilson,et al.  Widefield quantitative multiplex surface enhanced Raman scattering imaging in vivo , 2013, Journal of biomedical optics.

[34]  Christopher H Contag,et al.  A Raman-based endoscopic strategy for multiplexed molecular imaging , 2013, Proceedings of the National Academy of Sciences.

[35]  Bing Yan,et al.  SERS tags: novel optical nanoprobes for bioanalysis. , 2013, Chemical reviews.