Targeted molecular probes for imaging atherosclerotic lesions with magnetic resonance using antibodies that recognize oxidation-specific epitopes.

Area of Science:

• Cardiovascular Research
• Medical Imaging
• Nanotechnology

Background:

• Oxidized low-density lipoprotein (oxLDL) is crucial in atherosclerotic plaque development and instability.
• oxLDL is found within macrophages and lipid pools in atherosclerotic lesions.

Purpose of the Study:

• To evaluate the feasibility of magnetic resonance imaging (MRI) for atherosclerotic lesions.
• To utilize micelles containing gadolinium and oxidation-specific antibodies for targeted imaging.

Main Methods:

• Preparation and characterization of targeted micelles (MDA2, E06, IK17) and control micelles.
• Pharmacokinetic and biodistribution studies in wild-type and apolipoprotein E-deficient (apoE(-/-)) mice.
• 9.4 T MRI performed over 96 hours post-micelle administration.

Main Results:

• Targeted micelles (MDA2, E06, IK17) showed longer plasma half-lives in apoE(-/-) mice compared to controls.
• Maximal arterial wall uptake observed between 72-96 hours, with 125-231% signal enhancement.
• Confocal microscopy confirmed micelle accumulation within atherosclerotic lesions and macrophages.
• Specific targeting was validated by reduced signal after pre-injection of free antibody.

Conclusions:

• MRI with gadolinium-loaded micelles and oxidation-specific antibodies enables specific targeting of atherosclerotic lesions.
• The technique provides excellent image quality for visualizing oxidation-rich atherosclerotic plaques.