Diagnosis of brain tumors is often delayed, jeopardizing therapeutic outcomes. Improved early diagnosis by conventional magnetic resonance spectroscopy (MRS), in which a unique tumor bio-marker, choline is monitored, is currently limited to larger, untreatable tumors by poor sensitivity. We propose to develop ultra- fast 13C choline magnetic resonance molecular micro-imaging, capable of real-time in vivo monitoring of tumor choline metabolism, PASADENA, a new generation of ultra-sensitive, ultra-fast in vivo MR imaging techniques optimized in our Laboratory for use in oncology, provides an increased signal to noise over 10,000 fold. It is our goal to determine the efficacy of hyperpolarized PASADENA reagents, using ultra-fast multinuclear imaging techniques in rat models of malignant brain tumor. This will be accomplished through the following aims:
Aim 1 : Characterization of hyperpolarization of PASADENA reagents in vitro. 15N-choline, 13C-choline, and 13C-glucose will be polarized and imaged to determine the degree of polarization and confirm depolarization rates from the calculated T1 relaxation times. This will be accomplished using established techniques of polarization transfer and multinuclear imaging in vitro and in vivo in normal rat.
Aim 2 : Determine the uptake and kinetics of each PASADENA reagent in tumors in vivo. Using a conventional 9L brain tumor rat model, 13C and 15N MRI and MRS will be acquired after infusion of the PASADENA reagent. Through defined End-Points, uptake and kinetics for each metabolite will be compared in cross-sectional and longitudinal studies, to establish improved sensitivity of PASADENA compared to conventional MRI and histology.
Aim 3 : Determine the specificity of the PASADENA reagents. 13C and 15N MRI and MRS of PASADENA reagents will be acquired in the more aggressive 9L-VEGF+ rats and tumor localization, uptake, and kinetics will be compared with those measured in Aim 2 to determine the specificity of the parameters and for diagnosis of more aggressive brain tumors. By achieving these aims we expect to open a new era of real-time molecular imaging which when translated for human use will provide earlier diagnosis, staging and therapeutic monitoring and improved long-term survival for patients with malignant brain tumors.
|Salzillo, Travis C; Hu, Jingzhe; Nguyen, Linda et al. (2016) Interrogating Metabolism in Brain Cancer. Magn Reson Imaging Clin N Am 24:687-703|
|Zacharias, Niki M; McCullough, Christopher R; Wagner, Shawn et al. (2016) Towards Real-time Metabolic Profiling of Cancer with Hyperpolarized Succinate. J Mol Imaging Dyn 6:|
|Cassidy, M C; Chan, H R; Ross, B D et al. (2013) In vivo magnetic resonance imaging of hyperpolarized silicon particles. Nat Nanotechnol 8:363-8|
|Ross, Brian D (2013) High-field MRS in clinical drug development. Expert Opin Drug Discov 8:849-63|
|Zacharias, Niki M; Chan, Henry R; Sailasuta, Napapon et al. (2012) Real-time molecular imaging of tricarboxylic acid cycle metabolism in vivo by hyperpolarized 1-(13)C diethyl succinate. J Am Chem Soc 134:934-43|
|Bhattacharya, Pratip; Chekmenev, Eduard Y; Reynolds, Wanda F et al. (2011) Parahydrogen-induced polarization (PHIP) hyperpolarized MR receptor imaging in vivo: a pilot study of 13C imaging of atheroma in mice. NMR Biomed 24:1023-8|
|Ross, B D; Bhattacharya, P; Wagner, S et al. (2010) Hyperpolarized MR imaging: neurologic applications of hyperpolarized metabolism. AJNR Am J Neuroradiol 31:24-33|
|Perman, William H; Bhattacharya, Pratip; Leupold, Jochen et al. (2010) Fast volumetric spatial-spectral MR imaging of hyperpolarized 13C-labeled compounds using multiple echo 3D bSSFP. Magn Reson Imaging 28:459-65|
|Lingwood, Mark D; Siaw, Ting Ann; Sailasuta, Napapon et al. (2010) Continuous flow Overhauser dynamic nuclear polarization of water in the fringe field of a clinical magnetic resonance imaging system for authentic image contrast. J Magn Reson 205:247-54|
|Lisitza, Natalia; Muradian, Iga; Frederick, Eric et al. (2009) Toward 13C hyperpolarized biomarkers produced by thermal mixing with hyperpolarized 129Xe. J Chem Phys 131:044508|
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