Document Detail


Molecular imaging of angiogenic therapy in peripheral vascular disease with alphanubeta3-integrin-targeted nanoparticles.
MedLine Citation:
PMID:  20665780     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Noninvasive molecular imaging of angiogenesis could play a critical role in the clinical management of peripheral vascular disease patients. The alpha(nu)beta(3)-integrin, a well-established biomarker of neovascular proliferation, is an ideal target for molecular imaging of angiogenesis. This study investigates whether MR molecular imaging with alpha(nu)beta(3)-integrin-targeted perfluorocarbon nanoparticles can detect the neovascular response to angiogenic therapy. Hypercholesterolemic rabbits underwent femoral artery ligation followed by no treatment or angiogenic therapy with dietary L-arginine. MR molecular imaging performed 10 days after vessel ligation revealed increased signal enhancement in L-arginine-treated animals compared to controls. Furthermore, specifically targeted nanoparticles produced two times higher MRI signal enhancement compared to nontargeted particles, demonstrating improved identification of angiogenic vasculature with biomarker targeting. X-ray angiography performed 40 days postligation revealed that L-arginine treatment increased the development of collateral vessels. Histologic staining of muscle capillaries revealed a denser pattern of microvasculature in L-arginine-treated animals, confirming the MR and X-ray imaging results. The clinical application of noninvasive molecular imaging of angiogenesis could lead to earlier and more accurate detection of therapeutic response in peripheral vascular disease patients, enabling individualized optimization for a variety of treatment strategies.
Authors:
Patrick M Winter; Shelton D Caruthers; John S Allen; Kejia Cai; Todd A Williams; Gregory M Lanza; Samuel A Wickline
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine     Volume:  64     ISSN:  1522-2594     ISO Abbreviation:  Magn Reson Med     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2011-01-04     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  8505245     Medline TA:  Magn Reson Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  369-76     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Angiogenesis Inhibitors / administration & dosage*
Animals
Arginine / administration & dosage*
Drug Delivery Systems / methods
Integrin alphaVbeta3 / analysis*
Magnetic Resonance Imaging / methods*
Molecular Probe Techniques*
Nanoparticles / diagnostic use
Peripheral Arterial Disease / diagnosis*,  drug therapy*
Prognosis
Rabbits
Treatment Outcome
Grant Support
ID/Acronym/Agency:
R01 EB001704/EB/NIBIB NIH HHS; R01 EB001704-01/EB/NIBIB NIH HHS; R01 EB001704-03/EB/NIBIB NIH HHS; R01 EB01704/EB/NIBIB NIH HHS; R01 HL073646/HL/NHLBI NIH HHS; R01 HL073646/HL/NHLBI NIH HHS; R01 HL073646-02/HL/NHLBI NIH HHS; R01 HL073646-07/HL/NHLBI NIH HHS; U54 CA119342/CA/NCI NIH HHS; U54 CA119342/CA/NCI NIH HHS; U54 CA119342-01/CA/NCI NIH HHS; U54 CA119342-05/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Integrin alphaVbeta3; 94ZLA3W45F/Arginine
Comments/Corrections

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