Analysis of hyperpolarized dynamic 13C lactate imaging in a transgenic mouse model of prostate cancer.

This study investigated the application of an acquisition that selectively excites the [1-13C]lactate resonance and allows dynamic tracking of the conversion of 13C-lactate from hyperpolarized 13C-pyruvate at a high spatial resolution. In order to characterize metabolic processes occurring in a mouse model of prostate cancer, 20 sequential 3D images of 13C-lactate were acquired 5 s apart using a pulse sequence that incorporated a spectral-spatial excitation pulse and a flyback echo-planar readout to track the time course of newly converted 13C-lactate after injection of prepolarized 13C-pyruvate. The maximum lactate signal (MLS), full-width half-maximum (FWHM), time to the peak 13C-lactate signal (TTP) and area under the dynamic curve were calculated from the dynamic images of 10 TRAMP mice and two wild-type controls. The regional variation in 13C-lactate associated with the injected pyruvate was demonstrated by the peak of the 13C-lactate signal occurring earlier in the kidney than in the tumor region. The intensity of the dynamic 13C-lactate curves also varied spatially within the tumor, illustrating the heterogeneity in metabolism that was most prominent in more advanced stages of disease development. The MLS was significantly higher in TRAMP mice that had advanced disease.

[1]  R. Gillies,et al.  Why do cancers have high aerobic glycolysis? , 2004, Nature Reviews Cancer.

[2]  John M Pauly,et al.  Double spin-echo sequence for rapid spectroscopic imaging of hyperpolarized 13C. , 2007, Journal of magnetic resonance.

[3]  J. Rosen,et al.  Metastatic prostate cancer in a transgenic mouse. , 1996, Cancer research.

[4]  Jan Wolber,et al.  Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy , 2007, Nature Medicine.

[5]  Daniel B. Vigneron,et al.  Current and Potential Applications of Clinical 13C MR Spectroscopy , 2008, Journal of Nuclear Medicine.

[6]  S J Kohler,et al.  In vivo 13carbon metabolic imaging at 3T with hyperpolarized 13C‐1‐pyruvate , 2007, Magnetic resonance in medicine.

[7]  J. Kurhanewicz,et al.  Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer using 1H HR‐MAS spectroscopy of biopsy tissues , 2008, Magnetic resonance in medicine.

[8]  Jan Henrik Ardenkjaer-Larsen,et al.  Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis. , 2006, Cancer research.

[9]  Albert P. Chen,et al.  Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. , 2008, Cancer research.

[10]  F A Jolesz,et al.  Gradient-echo imaging considerations for hyperpolarized 129Xe MR. , 1996, Journal of magnetic resonance. Series B.

[11]  P. Carroll,et al.  Quantitative analysis of prostate metabolites using 1H HR‐MAS spectroscopy , 2006, Magnetic resonance in medicine.

[12]  R. Matusik,et al.  Prostate cancer in a transgenic mouse. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Robert J. Gillies,et al.  Causes and Consequences of Increased Glucose Metabolism of Cancers , 2008, Journal of Nuclear Medicine.

[14]  J. Ardenkjær-Larsen,et al.  Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Nelson Analysis of volume MRI and MR spectroscopic imaging data for the evaluation of patients with brain tumors , 2001, Magnetic resonance in medicine.

[16]  Peter Magnusson,et al.  13C imaging—a new diagnostic platform , 2005, European Radiology.

[17]  John M Pauly,et al.  Design of flyback echo‐planar readout gradients for magnetic resonance spectroscopic imaging , 2005, Magnetic resonance in medicine.

[18]  Tsuey-Ming Chen,et al.  Pathobiology of autochthonous prostate cancer in a pre‐clinical transgenic mouse model , 2003, The Prostate.

[19]  A. Heerschap,et al.  Characterization of human prostate cancer, benign prostatic hyperplasia and normal prostate by in vitro 1H and 31P magnetic resonance spectroscopy. , 1993, The Journal of urology.

[20]  L Zhao,et al.  Gradientecho imaging considerations for hyperpolarized ^ Xe MR , 1996 .

[21]  Michael Lustig,et al.  Pulse sequence for dynamic volumetric imaging of hyperpolarized metabolic products. , 2008, Journal of magnetic resonance.

[22]  John M Pauly,et al.  Hyperpolarized C‐13 spectroscopic imaging of the TRAMP mouse at 3T—Initial experience , 2007, Magnetic resonance in medicine.