The use of hyperpolarised 13C-MRI in clinical body imaging to probe cancer metabolism

Abstract

Metabolic reprogramming is one of the hallmarks of cancer and includes the Warburg effect, which is exhibited by many tumours. This can be exploited by positron emission tomography (PET) as part of routine clinical cancer imaging. However, an emerging and alternative method to detect altered metabolism is carbon-13 magnetic resonance imaging (MRI) following injection of hyperpolarised [1-13C]pyruvate. The technique increases the signal-to-noise ratio for the detection of hyperpolarised 13C-labelled metabolites by several orders of magnitude and facilitates the dynamic, noninvasive imaging of the exchange of 13C-pyruvate to 13C-lactate over time. The method has produced promising preclinical results in the area of oncology and is currently being explored in human imaging studies. The first translational studies have demonstrated the safety and feasibility of the technique in patients with prostate, renal, breast and pancreatic cancer, as well as revealing a successful response to treatment in breast and prostate cancer patients at an earlier stage than multiparametric MRI. This review will focus on the strengths of the technique and its applications in the area of oncological body MRI including noninvasive characterisation of disease aggressiveness, mapping of tumour heterogeneity, and early response assessment. A comparison of hyperpolarised 13C-MRI with state-of-the-art multiparametric MRI is likely to reveal the unique additional information and applications offered by the technique.

MRI techniques for immunotherapy monitoring

“…33 Furthermore, PET does not provide any information on downstream metabolic products or compartmentalization of the signal within the tissue and has relatively low spatial resolution. 34 MRI is a widely available clinical imaging tool with many strengths and potential to address some of the clinical challenges in assessing response to immunotherapy while overcoming many of the limitations of nuclear medicine imaging techniques as outlined above. MRI utilizes a range of sequences to probe tissue anatomy, microstructure, physiology, and function, generating excellent soft tissue contrast at high spatial resolution throughout the body.…”

“…The conversion of pyruvate to lactate in tissues, under the action of lactate dehydrogenase, can be imaged using the emerging clinical tool of hyperpolarized carbon-13 MRI (HP 13 C-MRI). 34 By applying the technique of dynamic nuclear polarization to 13 C-labeled endogenous metabolites, the signal-to-noise ratio can be increased by 10,000-100,000 fold, sufficient to allow the spatial distribution of the hyperpolarized 13 C-labeled imaging probe to be detected after intravenous injection, and the detection of the immediate metabolites formed from it dynamically over time. 78 Several 13 C-labeled imaging probes have been developed over the years for interrogating different aspects of the glucose metabolism pathway including [1- 13 C]pyruvate for imaging the kinetics of pyruvate-to-lactate conversion, 78 The 13 C-labeled bicarbonate (H 13 CO 3 − ) for detecting tumor pH in vivo, 79 and increased production of [1,[4][5][6][7][8][9][10][11][12][13] C 2 ]malate from the administered [1,4-13 C 2 ]fumarate as a surrogate biomarker of cell necrosis or tumor cell death in response to treatment 80 (figure 2).…”

“… 33 Furthermore, PET does not provide any information on downstream metabolic products or compartmentalization of the signal within the tissue and has relatively low spatial resolution. 34 …”

Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients

“…There are a number of potential biological factors contributing to the changes in hyperpolarized 13 C-label exchange between pyruvate and lactate following treatment (15). For example, the intracellular pyruvate concentration is determined by both tissue perfusion and membrane transport.…”

Deuterium metabolic imaging and hyperpolarized13C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism

“…Deuterium ( 2 H) metabolic imaging (DMI) and hyperpolarized carbon-13 metabolic MRI ( 13 C-HPMRI) are emerging techniques to probe dynamic changes in tissue metabolism using MRI without the use of ionizing radiation (Ardenkjær-Larsen et al, 2003; De Feyter et al, 2018; Vaeggemose et al, 2021; Woitek and Gallagher, 2021; Zaccagna et al, 2018). Due to the distinct biological and nuclear properties of these isotopes of hydrogen and carbon, metabolic pathways can be differentially probed using the two techniques.…”