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

彩色 MPI 作为一种体内评估磁性纳米颗粒动力学和结合的新方法

• 批准号: 10249102
• 负责人: Patrick Goodwill
• 金额: $ 80.24万
• 依托单位: MAGNETIC INSIGHT, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249102
• 关键词: Algorithms; Anatomy; Antibodies; Arterial Fatty Streak; Binding; Canada; Cardiovascular Diseases; Characteristics; China; Color; Development; Diagnosis; Discipline of Nuclear Medicine; Disease; Functional disorder; Goals; Grant; Human; Image; Imaging Device; Imaging technology; In Vitro; Indium-111; Liver; Lung; Magnetic Resonance Imaging; Magnetic nanoparticles; Magnetism; Malignant Neoplasms; Medical; Methods; Morphologic artifacts; Motion; Peptide antibodies; Phase; Physics; Physiologic pulse; Physiological; Production; Reporter; Research Personnel; Roentgen Rays; Sampling; Scanning; Scientist; Sensitivity and Specificity; Signal Transduction; Site; Stroke; Technology; Testing; Tissues; Tracer; Ultrasonography; Work; base; bioimaging; biomaterial compatibility; clinically translatable; commercialization; contrast imaging; image reconstruction; imager; imaging modality; improved; in vivo; in vivo evaluation; infancy; innovation; insight; iron oxide; malignant breast neoplasm; molecular imaging; mortality; nanoparticle; novel; particle; pre-clinical; reconstruction; superparamagnetism; targeted agent; vascular inflammation

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.

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 几十年来，研究人员一直试图提高癌症、心血管疾病和中风的对比度。 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方法。 称为彩色 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 举个例子，科学家可以发现一种可以结合的抗体。 特异性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 类似地，T2* 加权 MRI 中的动脉粥样硬化斑块也可以通过以下方式显示出来。 附着在核医学生产商身上的靶向抗体（例如 111-In、99mTc）​这是一个顽固的挑战。 降低这些方法的敏感性和特异性的是，未绑定的生产者数量大大超过了绑定的生产者 通常可以提高 100 倍，有效地掩盖病理生理学，这将是医学上的重大进步。 分子成像如果结合和未结合的生产者可以在图像中分开，因为对比度会提高 然而，在我们之前的研究中，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。 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 科学家和追随者将束缚态和非束缚态的粒子分开。

项目成果

Superferromagnetic Nanoparticles Enable Order-of-Magnitude Resolution & Sensitivity Gain in Magnetic Particle Imaging.

• DOI: 10.1002/smtd.202100796
• 发表时间: 2021-11
• 期刊: Small methods
• 影响因子: 12.4
• 作者: Tay ZW;Savliwala S;Hensley DW;Fung KLB;Colson C;Fellows BD;Zhou X;Huynh Q;Lu Y;Zheng B;Chandrasekharan P;Rivera-Jimenez SM;Rinaldi-Ramos CM;Conolly SM
• 通讯作者: Conolly SM

Non-radioactive and sensitive tracking of neutrophils towards inflammation using antibody functionalized magnetic particle imaging tracers.

• DOI: 10.7150/ntno.50721
• 发表时间: 2021
• 期刊: Nanotheranostics
• 作者: Chandrasekharan P;Fung KLB;Zhou XY;Cui W;Colson C;Mai D;Jeffris K;Huynh Q;Saayujya C;Kabuli L;Fellows B;Lu Y;Yu E;Tay ZW;Zheng B;Fong L;Conolly SM
• 通讯作者: Conolly SM