Imaging Hyperpolarized Lactate in Prostate Cancer

Take-Away Points

• ■ Major focus: Assessing reproducibility and diagnostic information from hyperpolarized [1-carbon 13 (¹³C)] pyruvate MRI in prostate cancer.

• ■ Key result: Conversion of [1-¹³C] pyruvate to [1-¹³C] lactate showed reproducible kinetics with increased amounts of lactate in higher Gleason grades of prostate cancer due to expression of monocarboxylate transporter 1 and loss of tumor suppressor PTEN.

• ■ Impact: Development of imaging and image processing workflow for larger clinical studies investigating metabolic imaging with hyperpolarized [1-¹³C] pyruvate MRI as a potential marker linked to gene expression in prostate cancer.

Prostate cancer encompasses a diverse spectrum of disease along a continuum from indolent to highly aggressive disease. Increased detection of prostate cancer through prostate-specific antigen and biopsy raises concerns about overtreatment of patients with indolent disease. Available approaches for determining risk of disease progression do not reliably distinguish indolent from aggressive disease in individual patients, complicating selection of appropriate treatment. Granlund and colleagues used MR spectroscopy to quantify conversion of hyperpolarized [1-carbon 13 (¹³C)] pyruvate to [1-¹³C] lactate in a small cohort of patients with prostate cancer. A subset of patients volunteered for repeat imaging studies to assess reproducibility of imaging data. The research team developed image analysis methods to correct for variability in data for pyruvate and lactate based on differences in perfusion, an essential step toward larger scale, multicenter clinical trials. Hyperpolarized MRI revealed regional heterogeneity of lactate production with levels of lactate increasing significantly from benign prostate to Gleason 3 to Gleason 4/5 prostate cancer. Time to maximum pyruvate and lactate signal in prostate tissue and maximum ratio of lactate to pyruvate did not differ in test or re-test studies, indicating that hyperpolarized [1-¹³C] pyruvate MRI could be used to monitor disease status in the same patient over time. Correlations with pathologic and genomic data showed elevated expression of the cell membrane transport protein, monocarboxylate transporter 1, in regions with increased signal from [1-¹³C] lactate. Data also suggested a correlation between loss of the tumor suppressor protein, PTEN, and elevated lactate in a prostate cancer. Because loss of PTEN results in activation of the phosphatidylinositol-3-kinase (PI3K) pathway, these results imply that MRI data for [1-¹³C] lactate could identify patients likely to benefit from drugs targeting PI3K. While validation of these findings requires larger studies and clinical follow-up, hyperpolarized [1-¹³C] pyruvate MRI shows promise as an important addition to risk stratification and clinical decision making in prostate cancer.

Highlighted Article

• Granlund KL, Tee S-S, Vargas HA, et al. Hyperpolarized MRI of human prostate cancer reveals increased lactate with tumor grade driven by monocarboxylate transporter 1. Cell Metab 2019;30:1–10. doi: 10.1016/j.cmet.2019.08.024.