Abstract 17845: Nitric Oxide Loaded Echogenic Liposomes Enhance Molecular Imaging of Atherosclerosis
Background: Microvascular inflammation is linked with atheroma development. Molecular imaging using targeted ultrasound contrast agents has been reported to detect inflammatory components. However, component localization may be underestimated due to lack of penetration of contrast agents throughout atheroma. We have previously demonstrated that echogenic liposomes (ELIP) containing a vasodilator, nitric oxide (NO), can improve penetration of contrast agents into atheroma. We extended this hypothesis to determine if pretreatment with NO-loaded ELIP improves targeted component imaging using a candidate inflammatory marker.
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, and were subdivided to receive ultrasound-facilitated pretreatment with standard ELIP or NO-ELIP. Arteries were sectioned and stained with anti-mouse antibody. The histologic distribution of ICAM-1 ELIP in the media was quantitated using Nuance multi-spectral imaging system and compared with intravascular ultrasound imaging.
Results: By histology, ICAM-1 expression was noted throughout the atherosclerotic wall. Without NO-ELIP pretreatment, limited ICAM-1 ELIP distribution was demonstrated either by histology or ultrasound imaging. Pretreatment with NO-ELIP enhanced delivery of ICAM-1 ELIP throughout the arterial wall, which corresponded to ultrasound highlighting.
Conclusions: A pretreatment strategy of NO-loaded ELIP plus ultrasound facilitates ICAM-1 ELIP delivery to the arterial wall. Histologic expression and ultrasound component enhancement correlated. This novel NO pretreatment strategy has the potential to improve targeted molecular imaging of atheroma.
- © 2013 by American Heart Association, Inc.