This S10 proposal aims at funding the purchase of a GE Diamond DNP Polarizer for clinical magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C agents, to be housed in the new Center for Integrated Metabolic Imaging (CIMI) at Memorial Sloan-Kettering Cancer Center. There is a great unmet need for more precise and versatile whole-body molecular imaging technologies, and the development of such means would have an enormous public-health impact. Hyperpolarized MRSI (HP- MRSI) is an emerging technology with the unique capacity to image a large variety of metabolic processes in near real-time in vivo and three-dimensionally. Based on the promising data from preclinical studies and the first clinical trial using hyperpolarized MRSI, it is expected that its clinical implementation will have a significant impact on many aspects of oncology, including the ability to elucidate disease mechanisms noninvasively, diagnose disease and its recurrence earlier, and stratify patients for appropriate treatment regimens more rapidly. The GE Diamond DNP Polarizer is the first and currently only commercially available polarizer for use in humans. Via its central installation in CIMI, we propose to make the Diamond Polarizer the nidus of innovation in a unique new facility equipped with the most cutting-edge clinical molecular imaging capabilities, including integrated whole-body MR-PET and multinuclear-capable MR scanners. This will, for the first time, allow the performance of combined HP-MRSI/MRI/PET imaging in human patients, enabling these methods to complement and cross-validate each other synergistically. We have assembled a multidisciplinary team of experts from basic science and clinical departments to successfully implement HP-MRSI and to target specific clinical questions using HP-MRSI and the unique combination of HP-MRSI/MRI/PET. Large patient populations, extensive patient databases, tissue databanks, routine molecular and genomic profiling of tumors, and the diversity and expertise of our clinical and basic science faculty will allow us to correlate the metabolic signatures identified with HP-MRSI with the molecular composition of tumors. This, in turn, will increase the chances of achieving the central goal of this application, which is to establish novel HP-MRSI biomarkers of cancer and its response to treatment.
|Cho, Andrew; Eskandari, Roozbeh; Miloushev, Vesselin Z et al. (2018) A non-synthetic approach to extending the lifetime of hyperpolarized molecules using D2O solvation. J Magn Reson 295:57-62|
|Miloushev, Vesselin Z; Granlund, Kristin L; Boltyanskiy, Rostislav et al. (2018) Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. Cancer Res 78:3755-3760|