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: 7491731
• 负责人: RONALD L WALSWORTH
• 金额: $ 20.05万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7491731
• 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(申请人提供)：本申请的广泛目标是开发一种基于超极化硅纳米颗粒的磁共振成像的新型分子成像探针，为测量和成像健康和疾病的生物过程提供一种新的工具。基于氧化铁纳米颗粒的造影剂已被广泛应用于磁共振成像中，用于检测特定的分子靶点以及标记细胞以进行细胞跟踪。然而，用于检测氧化铁纳米颗粒的传统方法存在一些问题，包括难以量化氧化铁浓度，以及难以在经历运动或自然信噪比(SNR)较低的区域检测造影剂。含有超极化核团的造影剂为克服这些问题提供了一种新的方法。使用超极化稀有气体进行肺部成像已经清楚地证明了超极化试剂成像的好处，它既能显著提高检测灵敏度，又能消除所有背景信号。最近，13C超极化代谢物的13C成像为快速代谢谱提供了一种方法。然而，使用的超极化试剂的核弛豫时间非常短，大多数13C试剂的核弛豫时间通常不到60 S，对于需要几个小时才能到达并结合目标的靶向分子探针的成像来说，这太短了。这项应用将使用硅或二氧化硅纳米颗粒，其中29Si适合快速超极化，并已显示出长达5小时的核弛豫时间。因此，我们提出了一项关于纳米硅的合成、生物功能化和超极化的计划。这种基于29Si的显像剂将为靶向分子成像、细胞跟踪和肿瘤检测提供强大和亟需的新工具。这一多学科计划将物理和生物医学科学联系起来，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，该计划符合R-21资助机制的条件。该计划的具体目标是：1.合成和功能化硅纳米颗粒，并表征其物理性质，包括尺寸、结构、核和电子弛豫时间、电子谱线形和光学性质。2.实现了高效的超极化纳米硅的动态核极化方法。3.评价纳米硅作为分子靶标和核磁共振显像剂的体外体模的性能。 相关性：最近，分子成像剂的磁共振成像提供了一种新的方法来研究体内的特定分子靶点，标记特定的细胞并允许跟踪它们，以及检测和诊断身体各种位置的肿瘤。尽管有广泛的潜在应用，但由常见的MRI分子成像剂引起的或与其相关的重大问题限制了它们的适用性。无毒、高选择性、高MRI可检测的分子显像剂的发展将为淋巴结、肠、肺和心脏肿瘤的成像提供强大和迫切需要的新工具。

项目成果

Synthesis of long T₁ silicon nanoparticles for hyperpolarized ²⁹Si magnetic resonance imaging.

• DOI: 10.1021/nn305462y
• 发表时间: 2013-02-26
• 期刊: ACS NANO
• 影响因子: 17.1
• 作者: Atkins, Tonya M.;Cassidy, Maja C.;Lee, Menyoung;Ganguly, Shreyashi;Marcus, Charles M.;Kauzlarich, Susan M.
• 通讯作者: Kauzlarich, Susan M.