An extraordinary new technique utilizing hyperpolarized 13C labeled probes has the potential to revolutionize the observation of key cellular metabolic processes non-invasively in vivo by MR. Proof-of-principle animal studies have demonstrated up to 40,000 fold polarization enhancements of 13C labeled pyruvate, providing sufficient signal for rapid imaging of the tumor metabolites alanine and lactate. In this collaborative project with GE Healthcare scientists, we aim to, for the first time, combine hyperpolarized 13C labeled probes such as pyruvate and acetate with high field human MR scanners, optimized rf receivers and fast spectroscopic imaging pulse sequences, to obtain an approximately 4 order of magnitude increase in sensitivity for 13C metabolic imaging of prostate cancer. The accurate detection and characterization of prostate cancer remains a major problem in the clinical management of individual prostate cancer patients and in monitoring therapy. While a combination of MRI and 1H MR spectroscopic imaging has shown great promise for improving prostate cancer detection and characterization prior to and following therapy, the value of this technique is currently limited by its coarse spatial and spectral resolution. The use of 13C labeled pyruvate, and acetate provide the potential to simultaneously assess changes in metabolic fluxes through multiple biochemical pathways (glycolysis, citric acid cycle and fatty acid synthesis) simultaneously. All three of these pathways have been shown to have metabolic perturbations associated with the evolution and progression of human prostate cancer. In a series of studies involving ex vivo HR-MAS spectroscopic analysis of intact human prostate biopsies, human prostate cell lines cultured with 13C labeled substrates, and transgenic mice injected with 13C labeled substrate we will; (1) determine the key 13C labeled metabolites that best identify the presence of prostate cancer and characterize its aggressiveness, and (2) determine the kinetics of incorporation of I3C labels into the key metabolites as well as, the T1 and T2 relaxation times of the I3C labeled metabolites. This data will be combined with specialized rf detectors, fast 13C spectroscopic imaging pulse sequences, and data reconstruction and analysis protocols to detect hyperpolarized 13C labeled metabolic imaging probes in preliminary studies of prostate cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB005363-01
Application #
6964914
Study Section
Special Emphasis Panel (ZEB1-OSR-C (M1))
Program Officer
Mclaughlin, Alan Charles
Project Start
2005-09-15
Project End
2009-08-31
Budget Start
2005-09-15
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$383,111
Indirect Cost
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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Larson, Peder E Z; Bok, Robert; Kerr, Adam B et al. (2010) Investigation of tumor hyperpolarized [1-13C]-pyruvate dynamics using time-resolved multiband RF excitation echo-planar MRSI. Magn Reson Med 63:582-91
Lupo, Janine M; Chen, Albert P; Zierhut, Matthew L et al. (2010) Analysis of hyperpolarized dynamic 13C lactate imaging in a transgenic mouse model of prostate cancer. Magn Reson Imaging 28:153-62

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