title: Characterization of early neovascular response to acute lung ischemia using simultaneous (19)F/ (1)H MR molecular imaging.
abstract: Angiogenesis is an important constituent of many inflammatory pulmonary diseases, which has been unappreciated until recently. Early neovascular expansion in the lungs in preclinical models and patients is very difficult to assess noninvasively, particularly quantitatively. The present study demonstrated that (19)F/(1)H MR molecular imaging with αvβ3-targeted perfluorocarbon nanoparticles can be used to directly measure neovascularity in a rat left pulmonary artery ligation (LPAL) model, which was employed to create pulmonary ischemia and induce angiogenesis. In rats 3 days after LPAL, simultaneous (19)F/(1)H MR imaging at 3T revealed a marked (19)F signal in animals 2 h following αvβ3-targeted perfluorocarbon nanoparticles [(19)F signal (normalized to background) = 0.80 ± 0.2] that was greater (p = 0.007) than the non-targeted (0.30 ± 0.04) and the sham-operated (0.07 ± 0.09) control groups. Almost no (19)F signal was found in control right lung with any treatment. Competitive blockade of the integrin-targeted particles greatly decreased the (19)F signal (p = 0.002) and was equivalent to the non-targeted control group. Fluorescent and light microscopy illustrated heavy decorating of vessel walls in and around large bronchi and large pulmonary vessels. Focal segmental regions of neovessel expansion were also noted in the lung periphery. Our results demonstrate that (19)F/(1)H MR molecular imaging with αvβ3-targeted perfluorocarbon nanoparticles provides a means to assess the extent of systemic neovascularization in the lung.
authors.affiliation: Department of Medicine, Washington University School of Medicine, 660 S. Euclid, Campus Box 8215, St. Louis, MO, 63110, USA, anne@dom.wustl.edu.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Schmieder
authors.forename: Kezheng
authors.initials: K
authors.lastname: Wang
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Angana
authors.initials: A
authors.lastname: Senpan
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Pan
authors.forename: Jochen
authors.initials: J
authors.lastname: Keupp
authors.forename: Shelton D
authors.initials: SD
authors.lastname: Caruthers
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
authors.forename: Baozhong
authors.initials: B
authors.lastname: Shen
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wagner
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000494:pharmacology*; D005466:Fluorocarbons / Q000494:pharmacology*; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007511:Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism; D007554:Isotopes / Q000494:pharmacology; D008171:Lung Diseases / Q000000981:diagnostic imaging / Q000378:metabolism; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D053758:Nanoparticles; D018919:Neovascularization, Physiologic; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D039302:Integrin alphaVbeta3; D007554:Isotopes
references.citation: J Appl Physiol (1985). 2006 Feb;100(2):587-93
references.pmid: 16210444
references.citation: Chest. 2007 Mar;131(3):874-879
references.pmid: 17356107
references.citation: PLoS One. 2011 Jan 20;6(1):e16062
references.pmid: 21283766
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Oct;299(4):L535-41
references.pmid: 20693319
references.citation: Cancer Res. 2003 Sep 15;63(18):5838-43
references.pmid: 14522907
references.citation: Lab Invest. 2012 Apr;92(4):636-45
references.pmid: 22330343
references.citation: Chin J Cancer Res. 2011 Jun;23(2):118-22
references.pmid: 23483098
references.citation: FASEB J. 2008 Aug;22(8):2758-67
references.pmid: 18362202
references.citation: FASEB J. 2008 Dec;22(12):4179-89
references.pmid: 18697838
references.citation: Circ Res. 1955 Jul;3(4):422-4
references.pmid: 14390726
references.citation: Magn Reson Med. 2011 Oct;66(4):1116-22
references.pmid: 21394779
references.citation: Magn Reson Med. 2005 Mar;53(3):621-7
references.pmid: 15723405
references.citation: Respiration. 2011;81(3):253-61
references.pmid: 21116108
references.citation: J Appl Physiol (1985). 2008 May;104(5):1470-5
references.pmid: 18323463
references.citation: Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 Jul-Aug;2(4):431-40
references.pmid: 20564465
references.citation: Contrast Media Mol Imaging. 2010 May-Jun;5(3):155-61
references.pmid: 20586031
references.citation: Am J Pathol. 1950 Mar;26(2):177-95
references.pmid: 15406250
references.citation: Am J Pathol. 2000 Jul;157(1):93-101
references.pmid: 10880380
references.citation: Am J Respir Crit Care Med. 2008 Sep 15;178(6):558-64
references.pmid: 18556624
references.citation: Circ Res. 1960 Mar;8:353-76
references.pmid: 13843454
references.citation: Magn Reson Med. 2007 Oct;58(4):725-34
references.pmid: 17899609
references.citation: Respir Res. 2010 Sep 29;11:132
references.pmid: 20920222
references.citation: J Clin Invest. 2004 Jun;113(12):1684-91
references.pmid: 15199403
references.citation: Gynecol Oncol. 1996 Aug;62(2):260-7
references.pmid: 8751559
references.citation: J Inflamm (Lond). 2013 Feb 11;10(1):6
references.pmid: 23394254
references.citation: J Appl Physiol (1985). 2011 Feb;110(2):538-44
references.pmid: 21148340
references.citation: Int J Cancer. 2007 May 1;120(9):1951-7
references.pmid: 17278104
references.citation: FASEB J. 2011 Mar;25(3):875-82
references.pmid: 21097518
references.citation: Pharmaceutics. 2012 Nov 07;4(4):563-89
references.pmid: 24300371
references.citation: Allergy. 2010 Aug;65(8):946-58
references.pmid: 20415716
references.citation: IEEE Trans Med Imaging. 2011 Jan;30(1):22-7
references.pmid: 20699209
references.citation: Invest Radiol. 2009 Jan;44(1):15-22
references.pmid: 18836386
references.citation: Biochem Soc Trans. 1991 Nov;19(4):835-8
references.pmid: 1794568
references.citation: J Vis Exp. 2013 Feb 08;(72):
references.pmid: 23425776
references.citation: FASEB J. 2009 Sep;23(9):2978-85
references.pmid: 19376816
references.citation: Int J Radiat Oncol Biol Phys. 2002 Nov 15;54(4):1202-9
references.pmid: 12419449
references.citation: Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2517-21
references.pmid: 7681600
references.citation: J Vasc Surg. 1997 Jun;25(6):1061-9
references.pmid: 9201167
references.citation: J Biol Chem. 2000 Jun 16;275(24):18337-43
references.pmid: 10751402