Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study

Background Hyperpolarized (HP) C-13-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP C-13-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera. Methods Six patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized C-13-pyruvate, where pyruvate-to-lactate conversion rate (k(PL)) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses. Results We observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean k(PL) value of 0.020 +/- 0.006 (s(-1)) and 0.026 +/- 0.000 (s(-1)) in bone (N = 4) and liver (N = 2) metastases, respectively. Overall, high k(PL) showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of k(PL) from 0.026 at baseline to 0.015 (s(-1)) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 +/- 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 +/- 0.9). Conclusions HP C-13-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative k(PL) values following treatment response at early time points. This first feasibility study supports future clinical studies of HP C-13-pyruvate MRI in the setting of advanced prostate cancer.