Due to increased screening using serum prostate specific antigen (PSA) and extended-template transrectal ultrasound (TRUS) guided biopsies, thousands of patients with prostate cancer are being identified at an earlier and, potentially, more treatable stage. However, the decision on how to manage prostate cancer poses a major dilemma for patients and their physicians, because prostate cancers demonstrate a tremendous range in biologic diversity and risk and are treated with a broad spectrum of approaches from "active surveillance" to aggressive surgical, radiation-based, and other focal therapies. Since current methods to characterize the extent and aggressiveness of individual cancers are inadequate, this has motivated research into new noninvasive imaging approaches to address these needs by providing biomarkers that can help in both therapeutic selection and monitoring. We have established a major prostate cancer imaging program at UCSF that has developed and applied high spatial resolution magnetic resonance imaging (MRI) and 1H MR spectroscopic imaging (MRSI) techniques to provide noninvasive quantitative biomarkers for the evaluation of individual prostate cancer patients. However, there remains a critical clinical need for more sensitive and specific imaging biomarkers of prostate cancer that at the time of diagnosis and after therapy could help in the decision process. An extraordinary new imaging technique, hyperpolarized 13C spectroscopy, utilizes metabolic substrates (molecules the body uses for fuel) and has shown great potential in animal models to provide new noninvasive imaging biomarkers of prostate cancer location, volume, and aggressiveness.

While preliminary hyperpolarized 13C MRS studies in animal models of prostate cancer suggest that hyperpolarized metabolic biomarkers can provide an assessment of prostate cancer and its response to therapy, these animal models do not represent the human situation accurately enough to best define the appropriate hyperpolarized MR biomarkers of clinical prostate cancer aggressiveness and response to therapy. In this PCRP Synergistic Idea Development proposal we bring together the unique expertise of three internationally recognized investigators to accomplish the goal of developing a realistic model of human prostate cancer and using it to identify hyperpolarized molecular imaging biomarkers for improved prostate cancer patient-specific treatment planning and early assessment of response to hormone and chemotherapy. This research is very innovative in that it provides, for the first time, a way to investigate new metabolic biomarkers and therapies for prostate cancer in a preclinical model using living human prostate tissues.

Once established, this realistic model of human prostate cancer will allow the testing of new prostate cancer therapies, and identification of new biomarkers of prostate cancer presence, aggressiveness, and response to therapy. Most importantly for patients, GE Healthcare will be commercializing this new imaging technology and the biomarkers identified in this grant could be used to directly benefit patients in the near future.