A molecularly targeted MRI T2 contrast agent, synthesized to maximize the spin-spin relaxation of surrounding tissue and biofluid protons is proposed. By building on previous work in our group, individual Fe304 nanocrystals will be geometrically optimized and lipid-passivated to maximize the T2 relaxation effect, specifically by maximizing the magnetic anisotropy parameters and rotational correlation time. Thus, given poor signal intensities when molecularly targeting low concentrations of pathogenic molecules, these target specific nanoparticles will provide the greatest possible signal intensity delta. In this fashion, we intend to improve on existing Fe3O4 nanoparticle T2 relaxation agents reported in the molecular imaging research literature. Finally, we propose to use our designed contrast agent to target cardiac transplant rejection, thereby complementing the agency goal of bridging physical sciences and life sciences to advance medical care. Specific Aims: 1) Synthesize/Functionalize; 2) Characterize; and 3) Detect our shape/surface altered, magnetically optimized, targeted T2 contrast agent to receptors expressed during cardiac transplant rejection (via MRI). Research Design and Methods: Organo-metallic precursors are decomposed at high temperatures to yield highly anisotropic custom magnetic nanoparticles. These magnetic nanoparticles will be functionalized with a lipid/antibody monolayer and characterized via transmission electron microscopy, X-ray diffraction, flow cytometry, superconducting quantum interference device magnetometry, nuclear magnetic resonance dispersion, and 1.5/4.7 T magnetic resonance imaging. Public Health Relevance: Acute rejection in cardiac transplant is a leading reason for post-surgery mortality and can result in mortality rates of 20% in the first year post-transplant and up to 15 % in subsequent years. Current standards for evaluating rejection involve examination of immune activation via biopsy, which is a highly invasive technique that demands significant post-transplant follow-up by the physician and commitment by the patients to endure routine biopsy procedures for the rest of their lives. Thus, the need for a non-invasive method to detect rejection episodes in cardiac transplant patients is especially acute.

F31EB006695

2007-06-01

2008-05-31