This proposed research career award builds on the principal investigator's work as an NIH fellow involving the use of magnetic resonance spectroscopy for the improved characterization of prostate cancer. Prostate cancer is a disease that afflicts one in five American men; however, it is difficult to predict those cancers that will spread (metastasize) and become life threatening from those that will remain indolent. Combined Magnetic Resonance Imaging and Spectroscopic Imaging (MRI/3D-MRSI) has demonstrated the ability to: improve the localization of prostate cancer within the gland; assess the extracapsular spread of the disease; and provide a measure of therapeutic response. As an NIH postdoctoral fellow, the principal investigator used MRI/3D-MRSI to study the metabolic effects of hormone ablation therapy in prostate cancer patients, and developed high resolution magic angle spinning (HR-MAS) techniques for the analysis of ex vivo prostate cancer tissues. The goal of this study is to better characterize the metabolic changes observed in vivo by MRSI and ex vivo by HR-MAS by improving their correlation with the underlying biochemical, morphologic, and genetic changes associated with the disease. To achieve these goals, we will use multidimensional HR-MAS techniques to identify new metabolic markers which can be exploited in vivo, and diffusion based experiments to learn more about the intracellular vs. extracellular distribution of prostate metabolites. Further, we will combine our HR-MAS findings with improved pathologic analysis to more accurately correlate specific metabolic profiles with prostate tissue type. Immunohistochemical assays will be performed to correlate metabolic profiles with other markers for cellular proliferation and apoptosis. We will also investigate the impact of zinc changes on citrate metabolism by assaying zinc levels in prostate tissues by atomic absorption spectrophotometry and zinc transporter gene expression using real-time reverse-transcriptase polymerase chain reaction analysis. These methods will then be used to learn more about changes in citrate metabolism under hormone dependent and independent conditions, using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The completion of the specific aims of this study will provide the principal investigator with the additional tools needed to develop his own independent cancer imaging research program. UCSF is a leading prostate cancer research center, with an NCI-designated comprehensive cancer center and prostate SPORE program. This excellent research environment combined with the extensive research experience of the mentor will greatly facilitate the completion of the goals set out in this proposal.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA096618-02
Application #
6619855
Study Section
Subcommittee G - Education (NCI)
Program Officer
Eckstein, David J
Project Start
2002-08-01
Project End
2007-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$124,998
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
Santos, Carissa F; Kurhanewicz, John; Tabatabai, Z Laura et al. (2010) Metabolic, pathologic, and genetic analysis of prostate tissues: quantitative evaluation of histopathologic and mRNA integrity after HR-MAS spectroscopy. NMR Biomed 23:391-8
Albers, Mark J; Butler, Thomas N; Rahwa, Iman et al. (2009) Evaluation of the ERETIC method as an improved quantitative reference for 1H HR-MAS spectroscopy of prostate tissue. Magn Reson Med 61:525-32
Tessem, May-Britt; Swanson, Mark G; Keshari, Kayvan R et al. (2008) Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer using 1H HR-MAS spectroscopy of biopsy tissues. Magn Reson Med 60:510-6
Swanson, Mark G; Keshari, Kayvan R; Tabatabai, Z Laura et al. (2008) Quantification of choline- and ethanolamine-containing metabolites in human prostate tissues using 1H HR-MAS total correlation spectroscopy. Magn Reson Med 60:33-40
Pels, Pieter; Ozturk-Isik, Esin; Swanson, Mark G et al. (2006) Quantification of prostate MRSI data by model-based time domain fitting and frequency domain analysis. NMR Biomed 19:188-97
Swanson, Mark G; Zektzer, Andrew S; Tabatabai, Z Laura et al. (2006) Quantitative analysis of prostate metabolites using 1H HR-MAS spectroscopy. Magn Reson Med 55:1257-64
Zektzer, Andrew S; Swanson, Mark G; Jarso, Samson et al. (2005) Improved signal to noise in high-resolution magic angle spinning total correlation spectroscopy studies of prostate tissues using rotor-synchronized adiabatic pulses. Magn Reson Med 53:41-8