In Vivo Hyperpolarized Carbon-13 Diffusion Weighted MRI Measures Lactate Metabolism and Transport in Prostate Cancer

Prostate cancer is a heterogeneous group of tumors ranging from clinicallyinsignificant to lethally malignant. The clinical management of prostate cancer is challenging due to the lack of accurate assessment of cancer aggressiveness. Hyperpolarized magnetic resonance imaging (MRI) has enabled real-time measurement of metabolism, and has shown great promise for cancer diagnosis, staging and assessing treatment response in both pre- clinical and clinical studies. Aggressive prostate cancer overproduces lactate and overexpresses MCT4, the transporter primarily responsible for lactate efflux, resulting in acidification of the extracellular space and conferring a poor prognosis. In this pilot study, hyperpolarized diffusion weighted MRI was used to elucidate the intra- and extracellular distribution of metabolites, which can infer lactate efflux, and tumor microstructural environment. Transgenic adenocarcinoma mouse prostate (TRAMP) models of different stages were injected with hyperpolarized pyruvate; then pyruvate and lactate were excited with a single- band spectral-spatial RF pulse, followed by a single-shot, double spin-echo flyback echo planar imaging (EPI) readout. Four b-values were acquired per metabolite, ranging from 25-1000 s • mm^-2. Data were corrected for RF utilization and fit voxel-wise to a monoexponential decay to generate apparent diffusion coefficient (ADC) maps for each metabolite. We found that the in vivo lactate ADC is close to the ex vivo extracellular ADC, rather than the intracellular ADC. We also found lactate ADC in late-stage tumors (0.65 ± 0.11 mm • s^−1 , n=4) is higher than early-stage (0.46 mm^2 • s^−1 , n=1), indicating there is increased lactate efflux in aggressive cancer. In conclusion, we demonstrated that hyperpolarized diffusion weighted MRI can provide insight into metabolite compartmentalization and lactate efflux in the prostate tumor, and potentially assess cancer aggressiveness and therapeutic changes in a rapid, non-invasive manner