Development of hyperpolarized silicon nanoparticles as molecular MRI agents

开发超极化硅纳米颗粒作为分子 MRI 试剂

• 批准号: 7363867
• 负责人: RONALD L WALSWORTH
• 金额: $ 27.92万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7363867
• 关键词: 2,4-Dinitrophenol; Animal Model; Binding; Biological; Biological Process; Cell Nucleus; Cells; Compatible; Contrast Media; Detection; Development; Diagnosis; Disease; Electrons; Exhibits; Funding Mechanisms; Future; Health; Heart; Hour; Hydrogen; Image; Imaging Device; Imaging Techniques; In Vitro; Individual; Intestines; Investigation; Label; Liquid substance; Location; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Metabolic; Methods; Modeling; Molecular; Molecular Probes; Molecular Target; Morphologic artifacts; Motion; Noble Gases; Noise; Nuclear; Nuclear Structure; Optics; Particle Size; Patients; Performance; Positron-Emission Tomography; Predisposition; Production; Property; Qualifying; Range; Rate; Relaxation; Research; Resolution; S Phase; Scanning; Science; Signal Transduction; Silicon; Solid; Solutions; Structure; Surface; Techniques; Temperature; Time; Weight; base; biocompatible polymer; chemical synthesis; electron density; experience; imaging probe; improved; interest; iron oxide; light scattering; lung imaging; lymph nodes; magnetic field; molecular imaging; multidisciplinary; nanoparticle; novel; particle; physical property; programs; rapid technique; size; tool; tumor

DESCRIPTION (provided by applicant): The broad objective of this application is to develop a novel molecular imaging probe based on MRI of hyperpolarized silicon nanoparticles, providing a novel tool for measuring and imaging biological processes in health and disease. Iron-oxide nanoparticle-based contrast agents have been used extensively in MRI to detect specific molecular targets as well as to label cells for cell tracking. However, traditional methods used for detecting iron-oxide nanoparticles suffer from several problems, including difficulty quantifying the iron- oxide concentration, and difficulty detecting the contrast agent in regions that undergo motion or have low native signal-to-noise ratio (SNR). Contrast agents containing hyperpolarized nuclei provide a novel method to overcome many of these problems. The use of hyperpolarized noble gases for lung imaging has clearly demonstrated the benefits of imaging hyperpolarized agents, providing both dramatically increased detection sensitivity as well as eliminating all background signals. Recently, 13C imaging of 13C-hyperpolarized metabolites has provided a method for rapid metabolic profiling. However, the very short nuclear relaxation times of hyperpolarized agents used, typically less than 60 s for most 13C agents, is much too short for the imaging of targeted molecular probes that require several hours to both reach and bind their targets. This application will employ Si or SiO2 nanoparticles, where the 29Si is suitable for rapid hyperpolarization and has been shown to exhibit nuclear relaxation times as along as 5 hours. We therefore propose a program for the synthesis, biological functionalization, and hyperpolarization of silicon nanoparticles. Such 29Si-based imaging agents will provide powerful and much needed new tools for targeted molecular imaging, cell tracking and the detection of tumors. This multidisciplinary program bridges the physical and biomedical sciences, with the potential to provide significant breakthrough research in molecular imaging and the treatment of patients with a variety of cancers. Thus this program qualifies for the R-21 funding mechanism. The Specific Aims of the program are: 1. Synthesize and functionalize silicon nanoparticles, and characterize their physical properties; including size, structure, nuclear and electron relaxation times, electron spectral lineshape, and optical properties. 2. Implement efficient Dynamic Nuclear Polarization methods for hyperpolarizing silicon nanoparticles. 3. Evaluate the performance of silicon nanoparticles as molecular targets and magnetic resonance imaging agent's in vitro phantoms.7. Relevance: Recently, MRI of molecular imaging agents have provided a novel way to study specific molecular targets in the body, label specific cells and allow them to be tracked, and detect and diagnose tumors in a wide variety of body locations. Despite a wide array of potential applications, significant problems caused by or related to common MRI molecular imaging agents limit their applicability. The development of non-toxic, highly-selective, highly-MRI-detectable molecular imaging agents will provide powerful and much needed new tools for the imaging of tumors of the lymph nodes, bowel, lung, and heart.

描述（由申请人提供）：本申请的广泛目标是基于超极化硅纳米颗粒的MRI开发一种新型的分子成像探针，为测量和成像健康和疾病中的生物学过程提供了一种新颖的工具。基于铁纳米颗粒的对比剂已在MRI中广泛使用，以检测特定的分子靶标以及标记细胞以进行细胞跟踪。然而，用于检测铁氧化铁纳米颗粒的传统方法遇到了几个问题，包括难以量化铁氧化物浓度，以及难以检测经历运动或天然信号噪声比（SNR）较低的区域中的对比剂。含有超极化核的对比剂提供了一种克服许多问题的新方法。使用超极化的贵重气体对肺成像清楚地表明了成像超极化剂的好处，这两者都大大提高了检测灵敏度以及消除所有背景信号。最近，13C氧化代谢物的13C成像为快速代谢分析提供了一种方法。然而，对于大多数13C代理来说，使用超极化剂的核松弛时间通常小于60 s，对于需要数小时需要几个小时才能达到并结合其靶标的靶向分子探针的成像太短了。该应用将采用SI或SIO2纳米颗粒，其中29SI适用于快速超极化，并且已显示出核弛豫时间至高5小时。因此，我们提出了一个用于硅纳米颗粒的合成，生物功能化和超极化的程序。这种基于29SI的成像剂将为靶向分子成像，细胞跟踪和肿瘤检测提供强大而急需的新工具。该多学科计划桥接了物理和生物医学科学，有可能在分子成像和各种癌症患者的治疗方面提供重大突破性研究。因此，该计划有资格获得R-21资金机制。该程序的具体目的是：1。合成和功能化硅纳米颗粒，并表征其物理特性；包括尺寸，结构，核和电子松弛时间，电子光谱线形和光学特性。 2。为超极化硅纳米颗粒实施有效的动态核极化方法。 3。评估硅纳米颗粒的性能作为分子靶标和磁共振成像剂的体外幻影。7。 相关性：最近，分子成像剂的MRI提供了一种研究体内特定分子靶标，标记特定细胞并允许跟踪它们的新方法，并在各种身体位置进行检测和诊断肿瘤。尽管有各种各样的潜在应用，但由常见MRI分子成像剂引起或与之相关的重大问题限制了其适用性。无毒，高度选择性，高度可检测的分子成像剂的发展将为淋巴结，肠，肺和心脏的肿瘤成像提供强大且急需的新工具。