Development of hyperpolarized silicon nanoparticles as molecular MRI agents

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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.