New tools to investigate tumor metabolism by NMR/MRI

[Display omitted] •Assessment of metabolic changes in tumor cells is crucial for staging cancer and for monitoring the therapeutic response.•In solid tumors the occurrence of an acidic pH in the extracellular region is a hallmark of the metabolic changes as predicted by the Warburg effect. MRI CEST...

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Published in:Journal of magnetic resonance (1997) 2022-05, Vol.338, p.107198-107198, Article 107198
Main Authors: Aime, Silvio, Longo, Dario Livio, Reineri, Francesca, Geninatti Crich, Simonetta
Format: Article
Language:English
Subjects:
CEST
Contrast Media
FFC-relaxometry
Humans
Hydrogen-Ion Concentration
Hyperpolarized 13C
Intracellular water residence time
Magnetic Resonance Imaging - methods
Magnetic Resonance Spectroscopy - methods
Neoplasms - diagnostic imaging
Tumour metabolism
Water
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Summary:[Display omitted] •Assessment of metabolic changes in tumor cells is crucial for staging cancer and for monitoring the therapeutic response.•In solid tumors the occurrence of an acidic pH in the extracellular region is a hallmark of the metabolic changes as predicted by the Warburg effect. MRI CEST with Iopamidol allows an accurate pH mapping.•Direct detection of the metabolic changes in tumor cells can be gained by using hyperpolarized C-13 labeledsubstrates. This task can be achieved also with the Parahydrogen Induced Polarization procedure.•Metabolic changes in tumor cells result in an increase of the water exchange rate across the cytoplasmicmembrane. The assessment of this important biomarker can be achieved by Relaxometry at low magnetic field strengths. Changes in metabolism is an hallmark that characterizes tumour cells from healthy ones. Their detection can be highly relevant for staging the tumor and for monitoring the response to therapeutic treatments. Herein it is shown the readout of these changes can be achieved either by assessing the pH of the extracellular space in the tumour region and by monitoring real time transformations of hyperpolarized C-13 labelled substrates. Mapping pH in a MR image is possible by measuring the CEST response of an administered contrast agent such as Iopamidol that can provide accurate measurements of the heterogeneity of tumour acidosis. Direct detection of relevant enzymatic activities have been acquired by using Pyruvate and Fumarate hyperpolarized by the incorporation of a molecule of para-H2. Finally, it has been found that the tumour transformation involves an increase in the water exchange rate between the intra- and the extra-cellular compartments. A quantitative estimation of these changes can be obtained by acquiring the longitudinal relaxation times of tissue water protons at low magnetic field strength on Fast Field Cycling Relaxometers. This finding has been exploited in an application devoted to the assessment of the presence of residual tumour tissue in the margins of the resected mass in breast conservative surgery.
ISSN:1090-7807
1096-0856
DOI:10.1016/j.jmr.2022.107198