Abstract 17488: Molecular Imaging of Atheroma Components in vivo Using Targeted Echogenic Immunoliposomes

Abstract

Background: We have demonstrated that nitric oxide-loaded echogenic immunoliposomes (NO-ELIP) can enhance delivery of targeted molecular imaging agents. We hypothesize that ultrasound-facilitated NO-ELIP treatment will improve anti-vascular cell adhesion molecule-1 (VCAM-1) conjugated ELIP penetration into atheroma (ATH) for better molecular imaging of ATH components.

Methods: NO-ELIP were prepared by a pressurization-freezing method. Gammaglobulin (IgG) conjugated ELIP and anti-VCAM-1-ELIP were compared. Following ATH formation in carotid and femoral arteries (n=20 segments) in atherosclerotic Yucatan miniswine, each artery was imaged using a 20-MHz intravascular ultrasound catheter, and IgG-ELIP or anti-VCAM-1-ELIP were injected with or without NO-ELIP pretreatment. NO-ELIP pretreatment was performed with or without Doppler ultrasound activation 5 minutes before targeted ELIP administration. Acoustic enhancement of atherosclerotic lesions in each group was quantitated using mean grayscale value (MGSV) and raw radio frequency (RF) data followed by 3D visualization.

Results: Acoustic enhancement of the inflammatory ATH was clearly observed both visually in 3D segments and quantitatively with anti-VCAM-1-ELIP (anti-VCAM-1: MGSV=11±1.4%, RF=25±3.7% vs. IgG: MGSV=4.5±0.8%, RF=9.1±1.1%). NO-ELIP pretreatment without Doppler ultrasound activation demonstrated no difference in acoustic enhancement (MGSV=11±1.5%, RF=30±5.1%). Anti-VCAM-1-ELIP following Doppler ultrasound-facilitated NO delivery further enhanced ATH determination (MGSV=22±2.3%, RF=46±4.6%).

Conclusion: This study demonstrates improved ultrasound molecular imaging of ATH components in vivo using anti-VCAM-1-ELIP with NO-ELIP pretreatment for enhanced targeted delivery efficiency. This novel NO pretreatment strategy with Doppler ultrasound activation has the potential to improve targeted molecular imaging of early ATH components.