Abstract 19959: Ultrasound-Facilitated Nitric Oxide Delivery Enhances in vivo Inflammatory Atheroma Detection Using Targeted Echogenic Immunoliposomes
Background: We have previously demonstrated that antibody-conjugated echogenic immunoliposomes (ELIP) can detect early inflammatory atheroma. We have developed nitric oxide (NO)-containing ELIP that can enhance endothelial permeability and allow enhanced uptake of different sized molecules into the arterial wall. We hypothesize that pretreatment of NO-ELIP with ultrasound activation will enhance uptake of rhodamine-labeled targeted ELIP into atheroma in an in-vivo model, allowing for improved component highlighting.
Methods: ELIP were prepared by hydration, sonication, freezing and lyophilization. Targeted ELIP were prepared by conjugating anti-intercellular adhesion molecule-1 (ICAM-1) antibodies. New Zealand white rabbits (N=12) were fed an atherogenic diet, followed by balloon denudation of the abdominal aorta. Following atheroma formation, rhodamine-labeled anti-ICAM-1-ELIP were injected with or without pretreatment with NO-ELIP 5 minutes prior to anti-ICAM-1-ELIP administration. Aortas were imaged with intravascular ultrasound, aortic walls manually segmented, and enhancement quantitated. The association of rhodamine-labeled targeted ELIP to the aortic wall was determined by fluorescent microscopy.
Results: Anti-ICAM-1-ELIP enhanced acoustic reflectivity of inflammatory atheroma by 8.9±3.1% with respect to baseline, and NO-ELIP pretreatment without Doppler ultrasound activation showed no additional acoustic enhancement (11.0±2.0%). Anti-ICAM-1-ELIP following NO treatment with Doppler ultrasound further enhanced highlighting of atheroma (20.0±3.6%). There was no highlighting of atheroma with IgG-ELIP (3.6±1.4%).
Conclusion: Ultrasound-facilitated NO delivery can effectively enhance atheroma permeability and improve anti-ICAM-1-ELIP targeting to inflammatory components. This NO pretreatment strategy has a potential to improve targeted molecular imaging for early atheroma detection.
- © 2010 by American Heart Association, Inc.