Development of hyperpolarized silicon nanoparticles as molecular MRI agents

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测量和成像提供一种新的工具。基于氧化铁纳米颗粒的造影剂已广泛用于MRI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，以及难以检测运动区域或具有低原生信噪比（SNR）的造反差剂。含有超极化核的造影剂为克服这些问题提供了一种新的方法。使用超极化惰性气体进行肺部成像已经清楚地证明了成像超极化试剂的好处，提供了显着提高的检测灵敏度以及消除所有背景信号。最近，13C超极化代谢物的13C成像为快速代谢谱分析提供了一种方法。然而，使用的超极化试剂的核弛豫时间非常短，大多数13C试剂通常不到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，这太短了。该应用将使用Si或SiO2纳米颗粒，其中29Si适合快速超极化，并且已显示出核弛豫时间长达5小时。因此，我们提出了硅纳米颗粒的合成、生物功能化和超极化的方案。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而急需的新工具。这个多学科项目连接了物理和生物医学科学，具有在分子成像和各种癌症患者治疗方面提供重大突破性研究的潜力。因此，该项目符合R-21资助机制。该计划的具体目标是：1。合成和功能化纳米硅，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性质。2. 实现超极化硅纳米粒子的高效动态核极化方法。3. 评价硅纳米颗粒作为分子靶点和磁共振成像剂的体外显像性能。

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.