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

Abstract

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.

Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized 13C magnetic resonance

“…The clinical potential of hyperpolarized MR is widely recognized, in particular in cancer research [63], and the first trial in patients using [1-13 C]pyruvate demonstrated that this technology can provide unique metabolic information for diagnostic purposes [64]. The foreseen applications in cardiac imaging and their expected impact in cardiology have been recently discussed [65][66][67].…”

Hyperpolarized 13 C MR metabolic imaging can detect neuroinflammation in vivo in a multiple sclerosis murine model

“…Altogether, our results demonstrate a potential for 13 C MRSI of HP [1-13 C]pyruvate as a neuroimaging method for assessment of inflammatory lesions. Because HP 13 C MRSI is clinically translatable (33) and expanding rapidly, this study is of high significance for future clinical trials not only on MS but also all neurological diseases presenting an inflammatory component (66). When used in conjunction with conventional MRI techniques, such a method would enhance diagnosis and help refine therapeutic regimens, which will ultimately improve clinical outcome and patient care.…”

“…These findings validate the potential of 13 C MRSI of hyperpolarized pyruvate for in vivo detection of neuroinflammation. cancerous lesions through the monitoring of the increased HP [1-13 C]pyruvate-to-lactate conversion, not only in preclinical cancer models but also in the clinical setting (33).…”

Probing the cardiac malate–aspartate shuttle non‐invasively using hyperpolarized [1,2‐13C2]pyruvate

“…17,[19][20][21][22] Furthermore, our group and others have recently demonstrated that MR measurement of [1-13 C]pyruvate and its metabolic intermediates can be performed in humans. 23,24 Translational work in pigs and rats has demonstrated that the use of hyperpolarized [2-13 C]pyruvate as a contrast agent can reveal 13 C signals from metabolites associated with the tricarboxylic acid (TCA) cycle. [1-13 C]Citrate has been observed directly, as has [5-13 C]glutamate, which is in exchange with the TCA cycle intermediate α-ketoglutarate (α-KG).…”