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

摘要：目前的生物医学成像方法对于诊断像这样的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 注射双组分​分子成像示踪剂的这些成像方法中的​：一种看不见的、生理的 附着在可见报告上的特定靶向剂(多肽、抗体等)。在这里，我们提出一种新的成像方法 一种名为彩色MPI的方法，它通过只看到那些示踪剂来提高分子成像的对比度 特异性地结合到患病组织上。举个例子，科学家可以发现一种结合抗体 特别是血管炎症部位，并产生靶向剂。这种抗体可以与一种 磁性纳米颗粒报告器(一种超顺磁性氧化铁SPIO)和组合示踪剂可以突出 磁共振T2加权像中的动脉粥样硬化斑块。同样，Her2阳性的乳腺癌可以通过以下方式发现 核医学记者的靶向抗体(例如，111-In，99mTc)。​是一个顽固的挑战， 降低这些方法的敏感性和特异性的是，未绑定记者的数量大大超过了绑定记者 记者，往往是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 分子成像，如果结合和非结合的记者可以在图像中分离，因为对比度将改善 戏剧性的。然而，目前的成像方式不能区分结合示踪剂和非结合示踪剂。在我们之前的 我们开发了一种革命性的、非侵入性的、高度敏感的成像方法，称为 磁粒子成像(MPI)，它展示了生物医学成像的突出前景。此外， MPI的独特物理学允许人们区分结合的和非结合的磁性纳米颗粒，尽管这 技术仍处于初级阶段，需要提高其健壮性才能成功商业化。 在这笔赠款中，我们建议将彩色MPI(c-MPI)开发到我们的商业临床前成像仪中，并使 科学家和临床医生将处于结合状态和非结合状态的粒子分开。

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.