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

摘要：当前的生物医学成像方法对于诊断高死亡率疾病是必不可少的，例如 癌症、心血管疾病和中风。几十年来，研究人员一直试图提高对比度 通过注射双组分分子成像示踪剂来实现这些成像方法：一种不可见的生理学示踪剂 附着在可见报道分子上的特异性靶向剂（肽、抗体等）。在这里我们提出了一种新的成像 称为 Color MPI 的方法，通过仅查看那些示踪剂来提高分子成像的对比度 特异性结合患病组织。举个例子，科学家可以发现一种结合的抗体 专门针对血管炎症部位并创建靶向剂。该抗体可以附着在 磁性纳米颗粒报告剂（超顺磁性氧化铁 SPIO）和组合示踪剂可以突出显示 T2* 加权 MRI 中的动脉粥样硬化斑块。同样，Her2 阳性乳腺癌可能通过以下方式发现： 附着于核医学报告基因的靶向抗体（例如 111-In、99mTc）。​一项顽强的挑战 降低这些方法的灵敏度和特异性的原因是未结合的报告基因数量大大超过了结合的报告基因 记者，通常放大100倍，有效地掩盖了病理生理学。这将是医学上的一大进步 分子成像如果结合和未结合的记者可以在图像中分开，因为对比度会提高 戏剧性地。然而，当前的成像方式无法区分结合的示踪剂和未结合的示踪剂。在我们之前的 在这项工作中，我们开发了一种革命性的、非侵入性的、极其灵敏的成像方法，称为 磁粒子成像（MPI）在生物医学成像方面显示出杰出的前景。此外， MPI 的独特物理特性允许人们区分结合和未结合的磁性纳米粒子，尽管这 该技术仍处于起步阶段，需要提高其稳健性才能成功商业化。 在这笔拨款中，我们建议将彩色 MPI (c-MPI) 开发为我们的商业临床前成像仪，并启用 科学家和临床医生将粒子分解为束缚态和非束缚态。

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.