Collaborative Research Optical and Dynamic Nuclear Polarization Approaches to Hyperpolarization of Nanoparticles for Molecular Imaging

这项研究的总体目标是使硅纳米颗粒具有针对常见癌症的功能，使用动态核极化(DNP)增强这些颗粒的核磁共振信号，并在体外表征超极化颗粒。这些都是朝着我们的总体目标迈出的重要一步，即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。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。研究人员已经证明，硅纳米颗粒可以被表面覆盖，其极化比室温玻尔兹曼极化提高三个数量级以上，29Si纳米颗粒自旋可以表现出500%的核弛豫倍S。研究人员还证明，通过改变颗粒大小，可以根据应用定制这个驰豫时间。本提案侧重于纳米颗粒的功能化，以靶向常见的癌细胞，并努力最大限度地提高和保留纳米硅颗粒在输送过程中的超极化。这些基于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迫切需要的新工具。该提案包括三个具体目标。第一个目标是开发可超极化的靶向硅纳米颗粒；第二个目标是开发高效的动态核极化；第三个目标是对超极化前后的功能化纳米颗粒进行标准的核磁共振和磁共振成像。

0932985Walsworth"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."The overall goal of the proposed research is to functionalize Si nanoparticles to target common cancers, enhance the NMR signal of these particles using dynamic nuclear polarization (DNP), and characterize the hyperpolarized particles in vitro. These are vital steps toward our overall objective of developing a novel molecular imaging probe based on MRI of hyperpolarized silicon nanoparticles, to provide a novel tool for measuring and imaging biological processes in health and disease. 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. The investigators have demonstrated that Si nanoparticles can be surface-coated, have their polarization enhanced by over three of orders of magnitude compared to room temperature Boltzmann polarization, and that the 29Si nanoparticle spins can exhibit nuclear relaxation times 500 s. Investigators have also shown that this relaxation time can be tailored for the application by modifying particle size. The present proposal focuses on functionalization of the nanoparticles to target common cancer cells and efforts to maximize and retain the hyperpolarization of the Si nanoparticles during delivery. Such 29Sibased imaging agents will provide powerful and much needed new tools for targeted molecular imaging, cell tracking and the detection of tumors. The proposal consists of three specific aims. The first aim is to develop targetable Si nanoparticles that can be hyperpolarized; the second aim is to develop high efficiency dynamic nuclear polarization; the third aim is to perform standard NMR and MRI on the functionalized nanoparticles, before and after hyperpolarization.