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

当前的生物医学成像方法对于诊断高死亡率疾病是不可或缺的， 癌症、心血管疾病和中风。几十年来，研究人员一直试图改善对比度， 通过注射双组分分子成像示踪剂：一种看不见的，生理上的， 特异性靶向剂（肽、抗体等）连接到可见的报告物。在这里，我们提出了一种新的成像方法， 一种称为彩色MPI的方法，通过只看到那些 与病变组织特异性结合。举个例子，科学家可以发现一种抗体， 特别是血管炎症部位并产生靶向剂。这种抗体可以连接到 磁性纳米颗粒报告物（超顺磁性氧化铁SPIO）和组合的示踪剂可以突出显示 T2* 加权MRI中的动脉粥样硬化斑块。类似地，Her 2阳性乳腺癌可以通过以下方式揭示： 附着于核医学报道分子的靶向抗体（例如，111-In，99mTc）。 一个顽固的挑战， 降低这些方法的灵敏度和特异性的一个重要原因是未结合的报道分子大大超过结合的报道分子 报道者，通常是100倍，有效地掩盖了病理生理学。这将是医学上的一个重大进步 如果结合的和未结合的报告分子可以在图像中分离，则分子成像，因为对比度将提高 戏剧性地。然而，目前的成像方式不能区分结合和未结合的示踪剂。在我们之前的 我们已经开发出一种革命性的，非侵入性的，灵敏的成像方法，称为 磁粒子成像（MPI），它显示了出色的承诺，为生物医学成像。而且 MPI的独特物理学允许人们区分结合的和未结合的磁性纳米颗粒，尽管这 该技术仍处于起步阶段，需要改进其稳健性以成功实现商业化。 在这项资助中，我们建议将彩色MPI（c-MPI）开发成我们的商业临床前成像仪， 科学家和临床医生将结合态和非结合态的粒子分开。

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.