Kurhanewicz Research Program
Kurhanewicz Lab: Prostate Cancer Imaging Research Group
Mission Bay campus
Byers Hall Building, Suite 203
1700 4th Street
San Francisco, CA 94158
Funding sources: NIH and DOD.
UCSF Prostate Cancer Imaging Program
The accurate characterization of prostate cancer is a major problem in the management of individual prostate cancer patients and in monitoring treatment effects. The UCSF Prostate Imaging Program was established by John Kurhanewicz, PhD and Daniel Vigneron, PhD to address this pressing need. This research program develops new magnetic resonance imaging methods to improve the assessment of prostate cancer. Kurhanewicz has directed the UCSF Prostate Imaging Program since 1998; the group has applied their advanced imaging techniques in over 6,500 research and clinical exams.
Utilizing Advanced Magnetic Resonance Imaging (MRI) in Patient Care
The program's translational multidisciplinary research projects range from basic magnetic resonance (MR) development to the implementation of what are now routine usages of MR imaging tools in the clinic. The program has developed a commercial multiparametric magnetic resonance imaging staging exam for prostate cancer patients, and with NIH funding, is optimizing and clinically validating this exam. This FDA-approved, non-invasive exam involves a combination of anatomic, metabolic, diffusion and perfusion imaging designed to better detect and characterize prostate cancer in individual patients. Program members are investigating the ability of multiparametric MR to detect and characterize the extent and aggressiveness of prostate cancer prior to therapy, to improve radiation treatment planning, to detect residual disease early after therapy and to predict clinical outcome.
Developing New Biomarkers of Prostate Cancer Presence, Aggressiveness and Response to Therapy
The NIH defines a biomarker as biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. There is a growing amount of published data demonstrating that metabolic biomarkers can significantly improve the clinical assessment of cancer in patients and the development of new biomarkers is a focus of the Prostate Imaging Program. The program uses multiparametric MR data to locate cancer tissues in prostate cancer patients who undergo a biopsy and/or radical prostatectomy. The resulting prostate tissue is then analyzed using a non-destructive spectroscopic technique (1H HR-MAS) that enhances spectral resolution and provides the concentrations of all of the metabolic biomarkers in the prostate tissue. The same tissue can then undergo pathologic, genomic and proteomic analysis, providing a unique platform for new biomarker discovery. With NIH funding, the program is interested in establishing new biomarkers of cancer aggressiveness and androgen sensitivity as well as companion biomarkers for new therapies. The success of the above biomarker discovery projects has resulted in the establishment of the UCSF Biomedical Nuclear Magnetic Resonance Facility, directed by Dr. Kurhanewicz, dedicated to biomarker discovery and clinical translation.
The Future of MRI of Prostate Cancer
A new direction for the program is the development and clinical translation of an extraordinary new molecular imaging technique utilizing hyperpolarized 13C labeled metabolic substrates that has the potential to revolutionize the way we use MR imaging in the risk assessment of prostate cancer patients. Hyperpolarized (HP) 13C MR allows rapid and noninvasive monitoring of dynamic pathway-specific metabolic and physiologic processes. Hyperpolarization, achieved through the dynamic nuclear polarization (DNP) technique, can provide unprecedented gains in sensitivity (10,000 – 100,000 fold increase) for imaging 13C-labeled bio-molecules that are endogenous, nontoxic, and nonradioactive. Metabolically active HP 13C -labeled compounds can be delivered to living systems where the substrate is metabolized and the products can be imaged in real time. The ability to detect down-stream metabolism, specifically the metabolic flux of HP 13C-pyruvate to lactate catalyzed by lactate dehydrogenase (LDH), has shown great potential for not only detecting prostate cancer, but also for assessing the aggressiveness (pathologic grade) of the cancer and response to therapy. The first DNP polarizer for human studies has been sited at UCSF, and we have successfully completed the first clinical trial of 13C MR metabolic imaging in patients with prostate cancer. Future clinical studies of HP 13C MR in patients with advanced prostate cancer are planned to investigate the clinical value of this technique, and new technical developments are underway to allow the assessment of metastatic prostate cancer.