Color MPI as a novel method for in vivo assessment of magnetic nanoparticle dynamics and binding

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Summary: Current biomedical imaging methods are indispensable for diagnosing high-mortality diseases like Cancer, Cardiovascular Disease and Stroke. For decades, researchers have attempted to improve the contrast of these imaging methods by injecting two-component ​molecular imaging tracers​: an invisible, physiologically specific targeting agent (peptide, antibody, etc) attached to a visible reporter. Here we propose a new imaging method, called Color MPI, that improves the contrast of molecular imaging by seeing only those tracers that bind specifically to a diseased tissue. As one example, a scientist could discover an antibody that binds specifically to sites of vascular inflammation and create a targeting agent. This antibody can be attached to a magnetic nanoparticle reporter (a superparamagnetic iron oxide SPIO) and the combined tracer can highlight atherosclerotic plaques in a T2*-weighted MRI. Similarly, Her2-positive breast cancer may be revealed by targeted antibodies attached to nuclear medicine reporters (e.g., 111-In, 99mTc). ​A stubborn challenge that reduces the sensitivity and specificity of these methods is that unbound reporters greatly outnumber bound reporters, often by 100-fold, effectively obscuring the pathophysiology. It would be a major advance in medical molecular imaging if bound and unbound reporters could be separated in the image, as contrast would improve dramatically. However, current imaging modalities cannot distinguish bound from unbound tracers. In our prior work we have developed a revolutionary, noninvasive, and exquisitely sensitive imaging method called Magnetic Particle Imaging (MPI), which shows outstanding promise for biomedical imaging. Moreover, the unique physics of MPI allows one to distinguish bound from unbound magnetic nanoparticles, although this technology is still in its infancy and requires improvements to its robustness for successful commercialization. In this grant, we propose to develop Color MPI (c-MPI) into our commercial pre-clinical imager and enable scientists and clinicians to unmix particles in bound and unbound states.