Magnetic resonance imaging (MRI) has become arguably the most important clinical imaging modality but it is less well suited for molecular and metabolic imaging because of its inherently low sensitivity. Solution phase nuclear dynamic polarization (DNP) technology can increase the sensitivity of standard NMR experiments by factors of 5000 to 25000. Such increases in sensitivity make it possible to perform molecular/functional imaging of other nuclei than 1H. The signal coming from any hyperpolarized nucleus will decay according to the spin-lattice relaxation time (T1) and one can anticipate having a detectable NMR signal for ~5T1. This poses a limitation on the biochemical processes that could be imaged and motivates the search for long T1 agents. Among the common spin 1/2 NMR active nuclei 89Y(III) has the longest T1 relaxation time (up to 600 seconds) rendering hyperpolarized yttrium-89 attractive as a potential in vivo imaging and spectroscopy probe. Our preliminary data indicated that Y(III)-complexes can be hyperpolarized with currently available commercial hardware. The goal of this project is to demonstrate that imaging of hyperpolarized Y- complexes is possible in vivo. We will first establish the optimal conditions for the DNP hyperpolarization of 89Y (Specific Aim 1). Y(III) complexes of two open chain (DTPA, TTHA) and four macrocyclic ligands, [DOTA, PCTA, DOTP, DOTA(AmP)4] will be prepared and hyperpolarized. Polarization enhancements and T1's of the complexes will be determined (Specific Aim 2). We will build a dual-tuned 89Y/1H coil for rats and develop a protocol to image the biodistribution of hyperpolarized Y(III) chelates. The samples will be hyperpolarized in the Hypersense """""""" DNP polarizer and the in vivo imaging experiments will be performed at 4.7T (Specific Aim 3). The extreme sensitivity of 89Y(III) to its chemical environment could be exploited in the design of sensitive probes to image and map physiological parameters such as pH, temperature, and other indices of metabolism in vivo.
Solution phase nuclear dynamic polarization (DNP) nuclear magnetic resonance (NMR) technology increases the sensitivity of standard NMR experiments by factors of 5000 to 25000 making MRI imaging of nuclei other than 1H feasible. The goal of this proposal is to demonstrate that imaging hyperpolarized yttrium-89-complexes is possible in vivo. Potential applications include the design and synthesis of sensitive probes to image and map physiological parameters such as pH, temperature, redox state and glucose levels in vivo.
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