title: Quantum dots targeted to vascular endothelial growth factor receptor 2 as a contrast agent for the detection of colorectal cancer.
abstract: We successfully labeled colorectal cancer in vivo using quantum dots targeted to vascular endothelial growth factor receptor 2 (VEGFR2). Quantum dots with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking. The resulting QD655-VEGFR2 contrast agent was applied in vivo to the colon of azoxymethane (AOM) treated mice via lavage and allowed to incubate. The colons were then excised, cut longitudinally, opened to expose the lumen, and imaged en face using a fluorescence stereoscope. The QD655-VEGFR2 contrast agent produced a significant increase in contrast between diseased and undiseased tissues, allowing for fluorescence-based visualization of the diseased areas of the colon. Specificity was assessed by observing insignificant contrast increase when labeling colons of AOM-treated mice with quantum dots bioconjugated to isotype control antibodies, and by labeling the colons of saline-treated control mice. This contrast agent has a great potential for in vivo imaging of the colon through endoscopy.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Carbary-Ganz
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Barton
authors.forename: Urs
authors.initials: U
authors.lastname: Utzinger
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics; D019073:HT29 Cells; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D045663:Quantum Dots; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
references.citation: Clin Cancer Res. 2008 Feb 1;14(3):731-41
references.pmid: 18245533
references.citation: Nat Rev Drug Discov. 2005 Feb;4(2):161-5
references.pmid: 15688078
references.citation: Mol Imaging Biol. 2011 Dec;13(6):1173-82
references.pmid: 21042865
references.citation: Int J Nanomedicine. 2011;6:1739-45
references.pmid: 21980236
references.citation: N Engl J Med. 2004 Dec 23;351(26):2704-14
references.pmid: 15616205
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12617-21
references.pmid: 12235356
references.citation: Nanomedicine. 2012 Feb;8(2):228-36
references.pmid: 21704593
references.citation: Eur J Cancer. 2000 Apr;36(6):748-53
references.pmid: 10762747
references.citation: Small. 2010 Jan;6(2):256-61
references.pmid: 19911392
references.citation: Nat Rev Cancer. 2008 Aug;8(8):579-91
references.pmid: 18596824
references.citation: N Engl J Med. 1996 Jan 18;334(3):155-9
references.pmid: 8531970
references.citation: Nat Biotechnol. 2004 Jan;22(1):93-7
references.pmid: 14661026
references.citation: Science. 2003 May 30;300(5624):1434-6
references.pmid: 12775841
references.citation: J Clin Oncol. 2005 Feb 10;23(5):1011-27
references.pmid: 15585754
references.citation: Gut. 2009 Feb;58(2):241-8
references.pmid: 18852257
references.citation: Eur J Cancer. 1998 Aug;34(9):1439-47
references.pmid: 9849429
references.citation: Gastrointest Endosc. 2012 Jun;75(6):1206-10
references.pmid: 22425271
references.citation: Cancer Res. 1995 Sep 15;55(18):3964-8
references.pmid: 7664263
references.citation: Endoscopy. 2013 Jun;45(6):469-77
references.pmid: 23580409
references.citation: Curr Opin Biotechnol. 2005 Feb;16(1):63-72
references.pmid: 15722017
references.citation: Cancer Sci. 2011 Jan;102(1):117-21
references.pmid: 21070475
references.citation: Gastroenterology. 1997 Jan;112(1):17-23
references.pmid: 8978337
references.citation: Nano Lett. 2008 Sep;8(9):2851-7
references.pmid: 18712930
references.citation: Curr Opin Gastroenterol. 2005 Jan;21(1):70-9
references.pmid: 15687888
references.citation: Nat Biotechnol. 2004 Feb;22(2):198-203
references.pmid: 14704683
references.citation: Nano Lett. 2006 Apr;6(4):669-76
references.pmid: 16608262
references.citation: Nat Methods. 2012 Jun 28;9(7):676-82
references.pmid: 22743772
references.citation: Cancer Biol Ther. 2010 Sep 1;10(5):438-47
references.pmid: 21108515
references.citation: Nat Rev Cancer. 2007 Sep;7(9):645-58
references.pmid: 17687385
references.citation: Nat Med. 2005 Jun;11(6):678-82
references.pmid: 15880117
references.citation: Nat Protoc. 2007;2(8):1998-2004
references.pmid: 17703211
references.citation: Nat Biotechnol. 2003 Jan;21(1):47-51
references.pmid: 12459736
references.citation: JAMA. 2008 Mar 5;299(9):1027-35
references.pmid: 18319413
references.citation: Bioconjug Chem. 2007 Mar-Apr;18(2):389-96
references.pmid: 17263568
references.citation: APMIS. 2013 Feb;121(2):95-104
references.pmid: 23030255
references.citation: Biotechnol Adv. 2010 Mar-Apr;28(2):199-213
references.pmid: 19969062
references.citation: Nat Biotechnol. 2003 Jan;21(1):41-6
references.pmid: 12459735
references.citation: Bioconjug Chem. 2010 Apr 21;21(4):604-9
references.pmid: 20369817
references.citation: Clin Cancer Res. 1996 Oct;2(10):1679-84
references.pmid: 9816116
references.citation: Radiology. 2010 May;255(2):442-50
references.pmid: 20413757
references.citation: Oncol Rep. 2012 Jun;27(6):1925-31
references.pmid: 22378320
references.citation: Cancer Res. 2007 Feb 1;67(3):1138-44
references.pmid: 17283148
references.citation: Biochem Biophys Res Commun. 2005 Jul 29;333(2):328-35
references.pmid: 15961063
references.citation: Cancer Biol Med. 2012 Sep;9(3):151-63
references.pmid: 23691472
references.citation: Gastroenterology. 2010 Feb;138(2):435-46
references.pmid: 19852961
references.citation: ACS Nano. 2009 Mar 24;3(3):502-10
references.pmid: 19243145
references.citation: Clin Exp Metastasis. 2012 Aug;29(6):573-83
references.pmid: 22484916
references.citation: Nat Biotechnol. 2004 Aug;22(8):969-76
references.pmid: 15258594
references.citation: CA Cancer J Clin. 2008 May-Jun;58(3):130-60
references.pmid: 18322143
references.citation: APMIS. 2011 Jul;119(7):449-59
references.pmid: 21635552