Molecular Targeted Functional, Cellular and Molecular Imaging of Atherosclerosis with Antibody-conjugated Superparamagnetic Particles Using Magnetic Resonance
R. Sharma, J.K. Katz, Y. Haik and C.J. Chen
FAMU-FSU College of Engineering, US
MRI, molecular imaging, contrast agents, atherosclerosis, thrombosis, mice
Background: Magnetic Resonance Imaging (MRI) is a powerful non-invasive technique that provides high-resolution anatomical images of biological tssue 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 will be imaged in vivo.
Aim 1 will develop and refine gadolinium-apoferritin nano-particles that have shown great potential as relaxivity agents for MR contrast studies. Aim 2 will image antibody-conjugated iron-oxide micro-beads (0.9 μm)). Aim 3 will apply these imaging strategies using high field strength MRI (11.7 T/21 T) to interrogate processes of inflammation and thrombosis in vascular models. Targeting will be accomplished with established and novel antibodies developed by phage display (against active forms of fibrin and glycoprotein IIbIIIa).
Methodology: Molecular imaging probes will be synthesized and their magnetic resonance properties fully characterized in vitro. Arterial wire-injury is associated with a sequence of molecular and cellular events that result in intimal hyperplasia and, in the apolipoprotein E-deficient mouse, results in accelerated atherosclerosis. This versatile model exhibits multiple molecular imaging targets whose spatial and temporal expression we established. These features, in conjunction with straight, superficial course of the femoral artery make it an ideal imaging target to examine the pathology of atherothrombosis non-invasively in vivo and to measure the effects of interventions such as administration of potent CC chemokine inhibition using a derived protein.
Opportunities: The method here may provide an important non-invasive means of mapping molecular and cellular events in mice. Genetically-modified mice have become the pre-eminent animal model for the study of atherosclerosis and this powerful technique will allow effects of interventions to be followed serially in vivo. Application of these techniques to other mouse models of pathology (such as tumor angiogenesis, inflammatory diseases etc.) is feasible. Significantly, all of the imaging agents proposed here are actually, or potentially compatible with translation into use in humans.
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Nanotech 2006 Conference Program Abstract