Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate

Metabolic imaging with hyperpolarized pyruvate was used to safely and noninvasively visualize prostate tumors in patients. The Hyperpolarized Prostate Cancer cells have a different metabolism than healthy cells. Specifically, they consume more pyruvate—a key component in glycolysis—than their normal counterparts. Nelson and colleagues therefore used a hyperpolarized form of pyruvate ([1-13C]pyruvate) to sensitively image increased levels of its product, [1-13C]lactate, as well as the flux of pyruvate to lactate. The [1-13C]pyruvate agent was used here in a first-in-human study in men with prostate cancer. Patients received varying doses of [1-13C]pyruvate that were found to be safe. These patients were then rapidly imaged with hyperpolarized 13C magnetic resonance (MR), which was able to provide dynamic (time course) information as well as three-dimensional (3D) (spatial) data at a single time point. Tumors were detected in all patients with biopsy-proven cancer. And, importantly, with 13C MR imaging (MRI), Nelson et al. were able to see cancer in regions of the prostate that were previously considered to be tumor-free upon inspection with other conventional anatomic imaging methods. With the ability to safely image tumor location and also follow tumor metabolism over time, hyperpolarized 13C MRI may be useful both for initial diagnosis and for monitoring therapy. Although the patients in this study had early-stage disease, the authors believe that [1-13C]lactate/[1-13C]pyruvate flux will only increase with tumor grade, making this imaging technology amenable to more advanced and aggressive cancers. Future studies will focus on optimizing agent preparation and delivery to ensure that this imaging technology can benefit patients in all clinical settings. This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo 13C MR data, it is possible to evaluate the distribution of agents such as [1-13C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-13C]lactate in tumor, with the ratio of [1-13C]lactate/[1-13C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect 13C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-13C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-13C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-13C]lactate/[1-13C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.