Relaxometric investigations addressing the determination of intracellular water lifetime: a novel tumour biomarker of general applicability

ABSTRACT

¹H 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.