CLINICAL TRANSLATION OF HYPERPOLARIZED 13C-UREA FOR CANCER MR MOLECULAR IMAGING

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PROJECT SUMMARY / ABSTRACT This Academic-Industry partnership aims to develop and translate new instrumentation and techniques for HP 13C-urea MR perfusion imaging alone and in combination with HP 13C-pyruvate to enable future clinical studies of patients with cancer, facilitating a more personalized approach to therapeutic selection and monitoring. The end product of this project will be new dDNP Spinlab polarizer hardware and methods capable of producing sterile, hyperpolarized compounds for first-in-man perfusion and combined perfusion and metabolic imaging through initial prostate cancer patient investigations. To accomplish this important project, we have assembled an exceptional academic and industrial team with expertise in pre-clinical and clinical cancer research, HP sterile compounding, HP MRI development, and industry product development to: Develop chemistry, agent hardware and methods of dissolution DNP for the production of sterile HP 13C-urea by itself and then in combination with sterile HP 13C-pyruvate (Aim 1). Develop and implement novel rapid volumetric 13C MR imaging methods for serial dynamic imaging of HP 13C-urea, 13C-pyruvate and its metabolites, with high temporal and spatial resolution (Aim 2). Preclinical Testing and SOP development required for FDA IND submission (Aim 3). Establish safety and imaging feasibility of first-in-man combined HP 13C-urea and 13C- pyruvate MR imaging studies in patients with prostate cancer (Aim 4). The clinical motivation for this academic-industry partnership is that prostate cancer management is severely limited by currently available clinical and imaging information required to select the most appropriate treatment for individual patients and to assess response to therapy or development of therapeutic resistance. Hyperpolarized (HP) 13C MRI is a paradigm shifting new MR molecular imaging technique that provides new measures to detect, characterize aggressiveness, and monitor therapy in order to improve cancer clinical trials and individualized patient care. The scientific premise for this project is that, with the success of phase 1 clinical trial of HP 13C-pyruvate imaging in prostate cancer patients, the proliferation of commercially available clinical polarizers, and the strong pre-clinical data demonstrating the potential value of HP 13C urea & pyruvate for advancing cancer imaging, the time is right for translating this new technology into the clinic and integrating it into current state-of-the-art imaging approaches. This Academic-Industry partnership is critical for robustly translating this novel imaging technology into the clinical arena, and UCSF and General Electric (GE) are uniquely positioned to accomplish this goal together. Although the novel hyperpolarized imaging tools and methods developed and disseminated in this academic- industrial partnership will initially be applied to patients with prostate cancer, they will have general applicability for a wide variety of cancers, and other human diseases.