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Hyperpolarized ¹³C Lactate, Pyruvate, and Alanine: Noninvasive Biomarkers for Prostate Cancer Detection and Grading

¹ Department of Bioengineering, University of California San Francisco and University of California Berkeley; ² Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California; ³ Sunny Brook Health Sciences Centre, Toronto, Ontario, Canada; ⁴ Union College, Schenectady, New York; and ⁵ GE Healthcare, Menlo Park, California

Requests for reprints: John Kurhanewicz, University of California San Francisco, Byers Hall, Room 203E, 1700 4th Street, San Francisco, CA 94158-2330. Phone: 415-514-9711; Fax: 415-514-4714; E-mail: John.Kurhanewicz{at}radiology.ucsf.edu.

Key Words: Hyperpolarized ¹³C • Pyruvate • Alanine • Lactate • Prostate Cancer • Glycolysis

An extraordinary new technique using hyperpolarized ¹³C-labeled pyruvate and taking advantage of increased glycolysis in cancer has the potential to improve the way magnetic resonance imaging is used for detection and characterization of prostate cancer. The aim of this study was to quantify, for the first time, differences in hyperpolarized [1-¹³C] pyruvate and its metabolic products between the various histologic grades of prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Fast spectroscopic imaging techniques were used to image lactate, alanine, and total hyperpolarized carbon (THC = lactate + pyruvate + alanine) from the entire abdomen of normal mice and TRAMP mice with low- and high-grade prostate tumors in 14 s. Within 1 week, the mice were dissected and the tumors were histologically analyzed. Hyperpolarized lactate SNR levels significantly increased (P < 0.05) with cancer development and progression (41 ± 11, 74 ± 17, and 154 ± 24 in normal prostates, low-grade primary tumors, and high-grade primary tumors, respectively) and had a correlation coefficient of 0.95 with the histologic grade. In addition, there was minimal overlap in the lactate levels between the three groups with only one of the seven normal prostates overlapping with the low-grade primary tumors. The amount of THC, a possible measure of substrate uptake, and hyperpolarized alanine also increased with tumor grade but showed more overlap between the groups. In summary, elevated hyperpolarized lactate and potentially THC and alanine are noninvasive biomarkers of prostate cancer presence and histologic grade that could be used in future three-dimensional ¹³C spectroscopic imaging studies of prostate cancer patients. [Cancer Res 2008;68(20):8607–15]

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