Potential Clinical Roles for Metabolic Imaging with Hyperpolarized [1-13C]Pyruvate

Serrao, Eva M.; Brindle, Kevin M.

doi:10.3389/fonc.2016.00059

Cited by 52 publications

(53 citation statements)

References 65 publications

(72 reference statements)

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“…In principle any small molecular probe can be hyperpolarized as long as they contain a nuclear spin, typically 13 C2021. Currently there is an large array of commercial available hyperpolarized of 13 C-labeled molecules which have been utilized in many different animal models of cancer2223, myocardial ischemia242526 and renal diseases27282930, and more recently in patients and healthy volunteers3132 Additionally, [1,4- 13 C]fumarate has been shown to be a reliable imaging biomarker for monitoring cellular necrosis33 in a rat model of xenograft tumors and subsequently in a rat model with folic acid-induced AKI34. These previous results showed an increased 13 C-malate signal in kidneys with progressive tubular necrosis.…”

mentioning

confidence: 99%

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

Nielsen

Eldirdiri

Bertelsen

et al. 2017

Sci Rep

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Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), and at present, there is a lack of reliable biomarkers that can diagnose AKI and measure early progression because the commonly used methods cannot evaluate single-kidney IRI. Hyperpolarized [1,4-13C2]fumarate conversion to [1,4-13C2]malate by fumarase has been proposed as a measure of necrosis in rat tumor models and in chemically induced AKI rats. Here we show that the degradation of cell membranes in connection with necrosis leads to elevated fumarase activity in plasma and urine and secondly that hyperpolarized [1,4-13C2]malate production 24 h after reperfusion correlates with renal necrosis in a 40-min unilateral ischemic rat model. Fumarase activity screening on bio-fluids can detect injury severity, in bilateral as well as unilateral AKI models, differentiating moderate and severe AKI as well as short- and long-term AKI. Furthermore after verification of renal injury by bio-fluid analysis the precise injury location can be monitored by in vivo measurements of the fumarase activity non-invasively by hyperpolarized [1,4-13C]fumarate MR imaging. The combined in vitro and in vivo biomarker of AKI responds to the essential requirements for a new reliable biomarker of AKI.

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confidence: 99%

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

Nielsen

Eldirdiri

Bertelsen

et al. 2017

Sci Rep

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“…The preferential ATP production via glycolysis of glucose to lactate leads to high lactate levels that some cancer cells can even exploit as a metabolic fuel (120)(121)(122). Conventionally, lactate can be observed and quantified by Magnetic Resonance Spectroscopy (MRS) or by the recently developed hyperpolarization technique (123)(124)(125)(126)(127)(128)(129). However, these methods are limited by low spatial resolution and long acquisition times.…”

Section: Imaging Lactatementioning

confidence: 99%

Non-invasive Investigation of Tumor Metabolism and Acidosis by MRI-CEST Imaging

Consolino¹,

Anemone²,

Capozza³

et al. 2020

Front. Oncol.

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Altered metabolism is considered a core hallmark of cancer. By monitoring in vivo metabolites changes or characterizing the tumor microenvironment, non-invasive imaging approaches play a fundamental role in elucidating several aspects of tumor biology. Within the magnetic resonance imaging (MRI) modality, the chemical exchange saturation transfer (CEST) approach has emerged as a new technique that provides high spatial resolution and sensitivity for in vivo imaging of tumor metabolism and acidosis. This mini-review describes CEST-based methods to non-invasively investigate tumor metabolism and important metabolites involved, such as glucose and lactate, as well as measurement of tumor acidosis. Approaches that have been exploited to assess response to anticancer therapies will also be reported for each specific technique.

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“…Furthermore, the quantification of various downstream metabolites, in addition to detecting and quantifying the uptake of the probe by hyperpolarized NMR, allows estimation of enzyme activity and the metabolic fluxes in central metabolic pathways, such as glycolysis and the tricarboxylic acid involved in tumors . Hyperpolarized NMR can also be used as a non‐invasive imaging modality for monitoring of tumor response to therapy …”

Section: Hyper‐polarized Nmrmentioning

confidence: 99%

Application of in vivo MR methods in the study of breast cancer metabolism

Jagannathan

2018

NMR in Biomedicine

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In the last two decades, various in vivo MR methodologies have been evaluated for their potential in the study of cancer metabolism. During malignant transformation, metabolic alterations occur, leading to morphological and functional changes. Among various MR methods, in vivo MRS has been extensively used in breast cancer to study the metabolism of cells, tissues or whole organs. It provides biochemical information at the metabolite level. Altered choline, phospholipid and energy metabolism has been documented using proton ( 1 H), phosphorus ( 31 P) and carbon ( 13 C) isotopes. Increased levels of choline-containing compounds, phosphomonoesters and phosphodiesters in breast cancer, which are indicative of altered choline and phospholipid metabolism, have been reported using in vivo, in vitro and ex vivo NMR studies. These changes are reversed on successful therapy, which depends on the treatment regimen given.Monitoring the various tumor intermediary metabolic pathways using nuclear spin hyperpolarization of 13 C-labeled substrates by dynamic nuclear polarization has also been recently reported. Furthermore, the utility of various methods such as diffusion, dynamic contrast and perfusion MRI have also been evaluated to study breast tumor metabolism. Parameters such as tumor volume, apparent diffusion coefficient, volume transfer coefficient and extracellular volume ratio are estimated. These parameters provide information on the changes in tumor microstructure, microenvironment, abnormal vasculature, permeability and grade of the tumor. Such changes seen during cancer progression are due to alterations in the tumor metabolism, leading to changes in cell architecture. Due to architectural changes, the tissue mechanical properties are altered; this can be studied using magnetic resonance elastography, which measures the elastic properties of tissues. Moreover, these structural MRI methods can be used to investigate the effect of therapy-induced changes in tumor characteristics. This review discusses the potential of various in vivo MR methodologies in the study of breast cancer metabolism.

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Potential Clinical Roles for Metabolic Imaging with Hyperpolarized [1-13C]Pyruvate

Cited by 52 publications

References 65 publications

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

Non-invasive Investigation of Tumor Metabolism and Acidosis by MRI-CEST Imaging

Application of in vivo MR methods in the study of breast cancer metabolism

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