Detection and Characterization of Treatment Emergent Neuroendocrine Prostate Cancer Using Hyperpolarized 13C Magnetic Resonance
Technical Report,15 Aug 2018,14 Aug 2019
University of California San Francisco United States
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The goal of this proposal is to discriminate biologically divergent treatment-emergent neuroendocrine prostate cancer NEPC from advanced adenocarcinoma based on the metabolic profile of NEPC tumors and to use real-time changes in metabolism to monitor therapeutic efficacy by using novel hyperpolarized HP 13C metabolic imaging techniques. In the 1st year of funding, our major activities focused on collating preliminary studies for Aims 1 and 2 to establish feasibility. To this end for Aim 1, the probes glutamine and acetate were optimized for hyperpolarization technique and tested in cells and baseline TRMAP studies. Correlative measures of NEPC presence were developed using ELISA and serum enzyme activities in addition to IHC quantification. Furthermore preliminary metabolic profiling of TRMAP tumors showed altered substrate utilization with the onset of CRPC further strengthening our hypothesis of metabolic adaptations with treatment resistance. For Aim2, we did exhaustive feasibility of labeling studies in biopsy samples, and for the first time showed viability and detected ex vivo measures of glycolytic activity.
- Medicine and Medical Research