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