Molecular targeted functional, cellular and molecular imaging of atherosclerosis with antibody-conjugated superparamagnetic particles using magnetic resonance

Background: Magnetic Resonance Imaging (MRI) is a powerful non-invasive technique that provides highresolution anatomical images of biological tissue based on their inherent physio-chemical properties. The signal from MRI can be modulated by contrast agents, which can be specifically directed to cells and molecules of interest, thereby providing an opportunity for targeted imaging. Aims: We propose to extend previous work that has used very high-resolution MRI to characterize atherosclerotic plaque in mice. Through targeted imaging of cells and molecules involved in mouse atherosclerosis, pathological processes and their response to interventions can be imaged in vivo. Aim 1 was to develop and refine gadoliniumapoferritin nano-particles that have shown great potential as relaxivity agents for MR contrast studies. Aim 2 was image antibody-conjugated iron-oxide micro-beads (0.9 μm)). Aim 3 was applied using these imaging strategies using high field strength MRI (11.7 T/21 T) to interrogate processes of inflammation and thrombosis in vascular models. Targeting can be accomplished with established and novel antibodies developed by phage display (against active forms of fibrin and glycoprotein IIbIIIa). Methods: Molecular imaging probes were synthesized and characterized in vitro. Arterial injury was associated with a sequence of molecular and cellular events that result in intimai hyperplasia and, in the apolipoprotein E-deficient mouse, results in accelerated atherosclerosis. Results: This model exhibited molecular imaging targets whose spatial and temporal expression was established. These features, in conjunction with straight, superficial course of the femoral artery makes it an ideal imaging target to examine the pathology of atherothrombosis noninvasively in vivo and to measure the effects of interventions. Conclusion: The approach of molecular imaging by using antibody-conjugated superparamagnetic contrast agents may provide unique opportunity of microimaging in clinical setup.