Development of hyperpolarized silicon nanoparticles as molecular MRI agents

描述（由申请人提供）：本申请的广泛目的是开发一种基于超极化硅纳米颗粒的MRI的新型分子成像探针，为测量和成像健康和疾病中的生物过程提供一种新工具。基于氧化铁纳米颗粒的造影剂已被广泛用于MRI中，以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一种克服许多这些问题的新方法。使用超极化惰性气体进行肺成像已经清楚地证明了成像超极化剂的益处，提供了显著增加的检测灵敏度以及消除所有背景信号。最近，13 C-超极化代谢物的13 C成像提供了一种快速代谢分析的方法。然而，所使用的超极化剂的非常短的核弛豫时间（对于大多数13 C剂通常小于60 s）对于需要几个小时才能到达并结合其靶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纳米颗粒，其中29 Si适合于快速超极化，并且已经显示出显示出沿着为5小时的核弛豫时间。因此，我们提出了一个程序的合成，生物功能化，和超极化的硅纳米粒子。这种基于29 Si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且急需的新工具。这个多学科计划连接物理和生物医学科学，有可能在分子成像和治疗各种癌症患者方面提供重大突破性研究。因此，该计划符合R-21供资机制的条件。该计划的具体目标是：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，电子光谱线型和光学性质。2.实现高效的动态核极化方法，用于超极化硅纳米颗粒。3.评价硅纳米粒子作为分子靶和磁共振成像剂的体外体模的性能. 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特定的分子靶点，标记特定的细胞并允许它们被跟踪，以及检测和诊断各种身体部位的肿瘤。尽管有广泛的潜在应用，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其适用性。无毒、高选择性、高MRI可检测的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。

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.