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（由申请人提供）：本申请的主要目标是开发一种基于超极化硅纳米颗粒MRI的新型分子成像探针，为健康和疾病中的生物过程的测量和成像提供一种新型工具。基于氧化铁纳米颗粒的造影剂已广泛用于 MRI 中，以检测特定分子目标以及标记细胞以进行细胞跟踪。然而，用于检测氧化铁纳米粒子的传统方法存在几个问题，包括难以量化氧化铁浓度，以及难以检测经历运动或具有低天然信噪比（SNR）的区域中的造影剂。含有超极化核的造影剂提供了克服许多这些问题的新方法。使用超极化惰性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，可以显着提高检测灵敏度并消除所有背景信号。最近，13C 超极化代谢物的 13C 成像提供了一种快速代谢分析的方法。然而，所使用的超极化试剂的核弛豫时间非常短，对于大多数 13C 试剂来说通常小于 60 秒，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太短了。该应用将采用 Si 或 SiO2 纳米粒子，其中 29Si 适合快速超极化，并且已被证明具有长达 5 小时的核弛豫时间。因此，我们提出了硅纳米粒子的合成、生物功能化和超极化的计划。这种基于 29Si 的成像剂将为靶向分子成像、细胞追踪和肿瘤检测提供强大且急需的新工具。这个多学科项目连接了物理和生物医学科学，有可能在分子成像和多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 资助机制的资格。该项目的具体目标是： 1. 合成和功能化硅纳米粒子，并表征其物理性质；包括尺寸、结构、核和电子弛豫时间、电子谱线形状和光学特性。 2.实施高效的动态核极化方法来超极化硅纳米粒子。 3. 评价硅纳米粒子作为分子靶标和磁共振成像剂体外模型的性能。7． 相关性：最近，分子成像剂的 MRI 提供了一种新的方法来研究体内的特定分子靶标、标记特定细胞并允许跟踪它们，以及检测和诊断身体各个部位的肿瘤。尽管具有广泛的潜在应用，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它们的适用性。无毒、高选择性、高 MRI 可检测分子成像剂的开发将为淋巴结、肠、肺和心脏肿瘤的成像提供强大且急需的新工具。

项目成果

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

用于超极化2-Si磁共振成像的长T-硅纳米颗粒的合成。

• 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.