Abstract
ABSTRACT1H Fast-Field Cycling NMR relaxometry is proposed as a powerful method to investigate tumour cell metabolism by measuring changes in cell water content and mobility across the cellular membrane. Measurements of intracellular water residence time in cultured cells were carried out by measuring T1 at fixed field (0.2 T) after the addition of a paramagnetic Gd complex (Prohance) at different concentrations in the external medium. Investigations on tumour cells (mammary adenocarcinoma TS/A) grown in normo- or hypoxic conditions or suspended in ‘hypo-osmotic’ solutions allowed us to demonstrate that both hypoxic and hypo-osmotic conditions cause a marked increase in water mobility as assessed by the elongation of T1. Conversely, the metabolic change caused by glutamine (an aminoacid essential for tumour growth) deprivation caused a water mobility decrease (shorter T1). These findings suggest that T1 measurements at low and variable magnetic field strengths, giving access to the assessment of intracellular water lifetime, can provide important information about tumour cell metabolism in real time and non-invasively.
Highlights
IntroductionWe reported that the 1/T1 NMRD profiles measured in vivo on implanted mammary tumours unequivocally report on the change of water amount and mobility in the pathological tissues [4]
Intracellular water lifetime (τ in) has been recently suggested as a new, promising cancer hallmark with the potential to discriminate metabolic and microenvironmental states of tumour cells and their changes with therapy [1]
In order to perform a quantitative analysis of water dynamics in the different cell lines and to establish its relationship with the FFC-NMR profile behaviour, the assessment of the cell membrane permeability is crucial
Summary
We reported that the 1/T1 NMRD profiles measured in vivo on implanted mammary tumours unequivocally report on the change of water amount and mobility in the pathological tissues [4] This result opens new horizons for the non-invasive evaluation of tumour metabolic phenotypes, by providing useful and more detailed information related to the metastatic propensity of the tumour. The quantitative determination of the cell membrane permeability of a murine breast cancer cell line (TS/A) [11,12] was carried out in vitro following an established relaxometric procedure [13,14,15,16] For this purpose, measurements were carried out at the magnetic field of 0.5 T in the presence of increasing amounts (5–40 mM) of the paramagnetic Gd-HPDO3A complex in the extracellular space of cellular suspensions.
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