title: Preclinical evaluation of Raman nanoparticle biodistribution for their potential use in clinical endoscopy imaging.
abstract: Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endoscopy. The use of an accessory Raman endoscope in conjunction with topically administered tumor-targeting Raman nanoparticles during a routine colonoscopy could offer a new way to sensitively detect dysplastic lesions while circumventing Raman's limited depth of penetration and avoiding systemic toxicity. In this study, the natural biodistribution of gold surface-enhanced Raman scattering (SERS) nanoparticles is evaluated by radiolabeling them with (64) Cu and imaging their localization over time using micropositron emission tomography (PET). Mice are injected either intravenously (IV) or intrarectally (IR) with approximately 100 microcuries (μCi) (3.7 megabecquerel (MBq)) of (64) Cu-SERS nanoparticles and imaged with microPET at various time points post injection. Quantitative biodistribution data are obtained as % injected dose per gram (%ID g(-1)) from each organ, and the results correlate well with the corresponding microPET images, revealing that IV-injected mice have significantly higher uptake (p < 0.05) in the liver (5 h = 8.96% ID g(-1); 24 h = 8.27% ID g(-1)) than IR-injected mice (5 h = 0.09% ID g(-1); 24 h = 0.08% ID g(-1)). IR-injected mice show localized uptake in the large intestine (5 h = 10.37% ID g(-1); 24 h = 0.42% ID g(-1)) with minimal uptake in other organs. Raman imaging of excised tissues correlate well with biodistribution data. These results suggest that the topical application of SERS nanoparticles in the mouse colon appears to minimize their systemic distribution, thus avoiding potential toxicity and supporting the clinical translation of Raman spectroscopy as an endoscopic imaging tool.
authors: Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, 318 Campus Drive, Stanford, CA 94305, USA.
authors: Cristina L
authors: CL
authors: Zavaleta
authors: Keith B
authors: KB
authors: Hartman
authors: Zheng
authors: Z
authors: Miao
authors: Michelle L
authors: ML
authors: James
authors: Paul
authors: P
authors: Kempen
authors: Avnesh S
authors: AS
authors: Thakor
authors: Carsten H
authors: CH
authors: Nielsen
authors: Robert
authors: R
authors: Sinclair
authors: Zhen
authors: Z
authors: Cheng
authors: Sanjiv S
authors: SS
authors: Gambhir
references: Nat Nanotechnol. 2008 Apr;3(4):216-21
references: 18654506
references: Toxicol Sci. 2008 Jan;101(1):4-21
references: 17602205
references: Nat Nanotechnol. 2007 Aug;2(8):469-78
references: 18654343
references: J Biochem Biophys Methods. 1986 Jun;12(5-6):349-54
references: 3734326
references: Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12371-6
references: 16116095
references: Biosens Bioelectron. 2009 Dec 15;25(4):826-31
references: 19765972
references: Bioconjug Chem. 2007 Jul-Aug;18(4):1155-62
references: 17602510
references: Eur J Nucl Med Mol Imaging. 2003 May;30(5):737-47
references: 12536244
references: Small. 2010 Oct 18;6(20):2222-9
references: 20862677
references: Methods Mol Biol. 2010;624:375-84
references: 20217609
references: Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009 May-Jun;1(3):264-71
references: 20049796
references: Histochem Cell Biol. 2008 Nov;130(5):845-75
references: 18825403
references: Nat Med. 2008 Apr;14(4):454-8
references: 18345013
references: Appl Spectrosc. 2003 Jan;57(1):20A-42A
references: 14610929
references: Int J Nanomedicine. 2008;3(2):151-67
references: 18686776
references: Nano Lett. 2008 Sep;8(9):2800-5
references: 18683988
references: Nat Biotechnol. 2008 Jan;26(1):83-90
references: 18157119
references: JAMA. 2008 Mar 5;299(9):1027-35
references: 18319413
references: Small. 2009 Sep;5(17):1997-2004
references: 19466710
references: Environ Sci Technol. 2008 Aug 15;42(16):6264-70
references: 18767697
references: J Biomed Opt. 2005 May-Jun;10(3):031113
references: 16229638
references: Mol Imaging. 2003 Jul;2(3):131-7
references: 14649056
references: J Biophotonics. 2009 Feb;2(1-2):81-90
references: 19343687
references: Arch Toxicol. 2010 Mar;84(3):183-90
references: 19936708
references: J Nucl Med. 2007 Sep;48(9):1511-8
references: 17704240
references: Biomaterials. 2010 Mar;31(8):2034-42
references: 20044133
references: Chem Cent J. 2009 Nov 20;3:16
references: 19930546
references: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13511-6
references: 19666578
references: Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 Jan-Feb;2(1):99-112
references: 20049834
references: J Am Chem Soc. 2008 Dec 24;130(51):17214-5
references: 19053187
references: Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5844-9
references: 18378895
references: PLoS One. 2009;4(4):e5206
references: 19367337
references: Photomed Laser Surg. 2008 Apr;26(2):83-90
references: 18341416
references: Front Biosci (Schol Ed). 2010 Jan 01;2:422-31
references: 20036958
references: Nanomedicine (Lond). 2009 Jun;4(4):401-10
references: 19505243