Prostate cancer is a major health concern in the United States with >240,000 new cases per year and >28,000 deaths. Due to increased screening using serum prostate specific antigen (PSA) and extended-template transrectal ultrasound (TRUS) guided biopsies, patients with prostate cancer are being identified at earlier and potentially more treatable stages. Unfortunately, the differentiation of clinically significant cancer from indolent disease is often not reliably determined using currently available clinical and imaging prognostic data. Also the ability to accurately image treatment response in metastatic prostate cancers is also a critically important unmet clinical need. Preliminary data strongly indicate that hyperpolarized 13C-pyruvate MRI using dynamic nuclear polarization (DNP) has the potential to dramatically improve prostate cancer clinical management. The goal of this Bioengineering Partnership project is to develop and translate new hyperpolarized carbon-13 MR metabolic imaging techniques to enable human prostate studies investigating for the first time cancer presence (defined by post-surgery histopathology), grade, and metastatic tumors with response to therapy. Preclinical studies and an NIH-supported White paper have clearly demonstrated the potential of this powerful method to detect abnormal metabolism through specific enzymatic pathways in cancer models with significant correlations to grade and treatment response. The dose-escalation Phase 1 safety trial that we recently completed demonstrated the safety and feasibility of using hyperpolarized [1-13C] pyruvate to detect not only its uptake in the prostate, but also its enzymatic conversion through LDH (up-regulated in cancer) to 13C-lactate in regions of suspected cancer. The research proposed in this BRP takes the critical next step in the clinical translation of hyperpolarized [1- 13C] pyruvate imaging of patients with prostate cancer. New techniques and patient studies are required to investigate its clinical potential and to extend this work to the study of metastatic disease sites for the first tme. While successful in demonstrating safety and "proof-of-concept" as designed, the small Phase 1 trial did not investigate clinical value and used rudimentary acquisition techniques. The proposed Bioengineering Research Partnership project is required to develop, translate, and apply new HP 13C MRI techniques for unprecedented "First-in-Man" investigations of the ability of HP 13C-pyruvate MR to address unmet clinical needs in the management of primary and metastatic prostate cancer patients. To accomplish this important project, we have assembled a highly-experienced multidisciplinary research team combining extensive expertise in MR bioengineering, hyperpolarized (HP) 13C research, advanced MRI data analysis, sterile pharmaceutical compounding, Urology, Oncology, Pathology, Radiology, and Investigational Therapeutics. The research facilities and environment includes the DNP polarizers, multiple MR systems and clinical research infrastructure required for successful completion of the proposed translational BRP project.

Public Health Relevance

The successful outcome of the proposed project will result in the development and translation into the clinical setting of new methods to enable greatly improved metabolic MR imaging of human prostate cancer. While this project focuses on prostate cancer, these new molecular imaging techniques could ultimately benefit the clinical management of other cancers and diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB017449-01
Application #
8573124
Study Section
Special Emphasis Panel (ZRG1-SBIB-N (55))
Program Officer
Liu, Guoying
Project Start
2013-08-15
Project End
2018-07-31
Budget Start
2013-08-15
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$1,190,965
Indirect Cost
$406,820
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Sriram, Renuka; Van Criekinge, Mark; DeLos Santos, Justin et al. (2016) Non-invasive differentiation of benign renal tumors from clear cell renal cell carcinomas using clinically translatable hyperpolarized (13)C pyruvate magnetic resonance. Tomography 2:35-42
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Shang, Hong; Skloss, Timothy; von Morze, Cornelius et al. (2016) Handheld electromagnet carrier for transfer of hyperpolarized carbon-13 samples. Magn Reson Med 75:917-22
Shang, Hong; Larson, Peder E Z; Kerr, Adam et al. (2016) Multiband RF pulses with improved performance via convex optimization. J Magn Reson 262:81-90
Feng, Yesu; Gordon, Jeremy W; Shin, Peter J et al. (2016) Development and testing of hyperpolarized (13)C MR calibrationless parallel imaging. J Magn Reson 262:1-7
Shin, Peter J; Larson, Peder E Z; Uecker, Martin et al. (2015) Chemical shift separation with controlled aliasing for hyperpolarized (13) C metabolic imaging. Magn Reson Med 74:978-89
Sriram, Renuka; Van Criekinge, Mark; Hansen, Ailin et al. (2015) Real-time measurement of hyperpolarized lactate production and efflux as a biomarker of tumor aggressiveness in an MR compatible 3D cell culture bioreactor. NMR Biomed 28:1141-9

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