Hyperpolarized (HP) carbon-13 MRI has demonstrated the ability to significantly advance our understanding of disease processes and the great potential to become a cost effective molecular imaging tool for monitoring clinical trial and individual patient management. Our recent first-in-man Phase 1 Clinical Trial utilized unique dissolution DNP instrumentation and methods for [1-13C] pyruvate metabolic imaging. The proposed project is designed to take a major step forward by developing new instrumentation and methods to translate preclinical multi-agent polarization studies into first-in-man dual-agent simultaneous metabolic &perfusion HP MRI studies. This project aims to develop a new MRI approach to characterize cancers based on their genetic/proteomic and perfusion abnormalities and apply this method in preclinical models to obtain the required preliminary data for FDA approval and then to conduct initial human studies. Hyperpolarized (HP) carbon-13 MRI is a powerful new molecular imaging method which uses specialized instrumentation to provide signal enhancements of over 5-orders of magnitude for carbon-13 enriched, safe, endogenous, non-radioactive compounds. Co-polarization of 13C-urea with [1-13C] pyruvate provides not only an internal reference for improved quantitative accuracy, but also a method for simultaneous perfusion measurements without ionizing radiation and without the nephrotoxicity effects of other perfusion contrast agents. This project aims to translate and perform first-in-man HP dual-agent perfusion &metabolic MRI to address a pressing clinical need, specifically improved radiological characterization of prostate cancer aggressiveness and treatment response. New hardware/instrumentation will be designed and constructed to enable dual-agent functionality necessary for first-in-man hyperpolarized perfusion and metabolic imaging human studies. Novel MRI acquisition and analysis methods will also be developed for acquiring rapid high resolution metabolic &perfusion imaging data. The techniques developed in this project will be applied in prostate cancer patients to address a clear unmet clinical need. However, these dual-agent HP 13C MR techniques also have general applicability to advance the clinical research of other cancers and potentially a wide range of pathologies including cardiac, liver, and kidney disease.

Public Health Relevance

The successful outcome of the proposed project will result in the development of new instrumentation and methods for dual-agent MR molecular imaging of both perfusion and metabolism simultaneously. This project also includes translation into the clinical setting with a first-ever feasibility study of these methods in prostate cancer patients. 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 #
1R01EB013427-01A1
Application #
8585007
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Liu, Guoying
Project Start
2013-07-15
Project End
2017-05-31
Budget Start
2013-07-15
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$704,365
Indirect Cost
$255,725
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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von Morze, Cornelius; Carvajal, Lucas; Reed, Galen D et al. (2014) Directly detected (55)Mn MRI: application to phantoms for human hyperpolarized (13)C MRI development. Magn Reson Imaging 32:1165-70
von Morze, Cornelius; Bok, Robert A; Reed, Galen D et al. (2014) Simultaneous multiagent hyperpolarized (13)C perfusion imaging. Magn Reson Med 72:1599-609
Reed, Galen D; von Morze, Cornelius; Bok, Robert et al. (2014) High resolution (13)C MRI with hyperpolarized urea: in vivo T(2) mapping and (15)N labeling effects. IEEE Trans Med Imaging 33:362-71