Development and Translation of Hyperpolarized C-13 Prostate Cancer MRI Methods

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Project Summary/Abstract This Bioengineering Research Partnership has been designed to develop new techniques to perform primary and especially metastatic prostate cancer patient HP 13C MRI exams with the goal of creating a robust, reliable exam with 2-fold higher SNR, 5-fold higher spatial coverage, and new metabolic information from C-2 pyruvate to benefit prostate cancer research, clinical trials evaluating new treatments, and ultimately patient care. Preliminary studies have demonstrated the ability of dynamic HP 13C MR to detect upregulated LDH-catalyzed pyruvate to lactate conversion in aggressive prostate cancers and also to measure a dramatic reduction following successful therapy. While “proof-of-principle” has been shown in these initial studies, new bioengineering developments, hardware, and software are required to create a robust, cost-effective HP 13C MRI exam to fulfill clinical unmet needs. The current techniques are not robust, well-characterized tools ready to be widely applied. This BRP, with its specialized multidisciplinary research team, is designed to accomplish the required bioengineering developments and patient clinical research needed to refine, test and disseminate these new techniques & hardware following the NIH guidelines for scientific rigor, transparency and reproducibility. Specifically, we aim to: 1) Improve HP Pharmacy Methods for Producing Sterile HP 13C-pyruvate; 2) Develop New Robust HP 13C MR Technology for Primary Prostate Cancer; and 3) Specific Technical Developments for Metastatic Prostate Cancer Exam. New robust acquisition and analysis techniques will be developed and tested in pre-prostatectomy patients with the correlation of kPL & kPG conversion rate constants to step-section histopathology as the gold standard. Also the new methods will be applied in studies of patients with metastases to lymph nodes and pelvic bone to investigate their ability to detect therapy response/resistance for individual patients and future clinical trials of emerging pharmaceutical strategies. While focused on prostate cancer, the proposed BRP aims to develop new HP 13C metabolic imaging techniques that will ultimately benefit the clinical management of a wide variety of diseases. All techniques, hardware designs, pharmacy methods, open-source software, and anonymized patient data from this BRP project will be disseminated to all interested sites continuing this BRP’s active dissemination methods to over 20 sites thus far in order to accelerate the tempo and improve the clinical impact of this powerful molecular imaging approach.