title: Nitric oxide improves molecular imaging of inflammatory atheroma using targeted echogenic immunoliposomes.
abstract: OBJECTIVE
  This study aimed to demonstrate whether pretreatment with nitric oxide (NO) loaded into echogenic immunoliposomes (ELIP) plus ultrasound, applied before injection of molecularly targeted ELIP can promote penetration of the targeted contrast agent and improve visualization of atheroma components.
  
  
  METHODS
  ELIP were prepared using the pressurization-freeze method. Atherosclerosis was induced in Yucatan miniswine by balloon denudation and a hyperlipidemic diet. The animals were randomized to receive anti-intercellular adhesion molecule-1 (ICAM-1) ELIP or immunoglobulin (IgG)-ELIP, and were subdivided to receive pretreatment with standard ELIP plus ultrasound, NO-loaded ELIP, or NO-loaded ELIP plus ultrasound. Intravascular ultrasound (IVUS) data were collected before and after treatment.
  
  
  RESULTS
  Pretreatment with standard ELIP plus ultrasound or NO-loaded ELIP without ultrasound resulted in 9.2 ± 0.7% and 9.2 ± 0.8% increase in mean gray scale values, respectively, compared to baseline (p < 0.001 vs. control). Pretreatment with NO-loaded ELIP plus ultrasound activation resulted in a further increase in highlighting with a change in mean gray scale value to 14.7 ± 1.0% compared to baseline (p < 0.001 vs. control). These differences were best appreciated when acoustic backscatter data values (RF signal) were used [22.7 ± 2.0% and 22.4 ± 2.2% increase in RF signals for pretreatment with standard ELIP plus ultrasound and NO-loaded ELIP without ultrasound respectively (p < 0.001 vs. control), and 40.0 ± 2.9% increase in RF signal for pretreatment with NO-loaded ELIP plus ultrasound (p < 0.001 vs. control)].
  
  
  CONCLUSIONS
  NO-loaded ELIP plus ultrasound activation can facilitate anti-ICAM-1 conjugated ELIP delivery to inflammatory components in the arterial wall. This NO pretreatment strategy has potential to improve targeted molecular imaging of atheroma for eventual true tailored and personalized management of cardiovascular diseases.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Hyunggun
authors.initials: H
authors.lastname: Kim
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Kee
authors.forename: Yonghoon
authors.initials: Y
authors.lastname: Rim
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Moody
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Klegerman
authors.forename: Deborah
authors.initials: D
authors.lastname: Vela
authors.forename: Shao-Ling
authors.initials: SL
authors.lastname: Huang
authors.forename: David D
authors.initials: DD
authors.lastname: McPherson
authors.forename: Susan T
authors.initials: ST
authors.lastname: Laing
mesh_terms: D000162:Acoustics; D000818:Animals; D006949:Hyperlipidemias; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry*; D057054:Molecular Imaging / Q000295:instrumentation / Q000379:methods*; D009569:Nitric Oxide / Q000737:chemistry*; D010539:Permeability; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D011897:Random Allocation; D013552:Swine; D013556:Swine, Miniature; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D008081:Liposomes; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide
keywords: Atherosclerosis; Contrast agent; Molecular imaging; Nitric oxide; Ultrasound