TmDOTP has become the most frequently used hyperfine NMR shift reagent for in vivo sodium NMR spectroscopy. It provides a good separation of the intracellular and extracellular sodium resonances and is well tolerated by animals.
Nuclear magnetic resonance spectroscopy is a non-destructive diagnostic tool to study the role of metal ions in cells and tissues. With lanthanide shift reagents it is possible to resolve the intracellular and extracellular cation NMR signals in cells and tissues. Paramagnetic lanthanide shift reagents for NMR active physiological alkali metal ions are thermodynamically stable, chemically inert, possess a net negative charge at physiological pH, are membrane impermeable and induce chemical shifts in the extracellular cation resonances sufficient to clearly resolve them from the intracellular cation resonances. The most commonly used biological shift reagents include dysprosium(III) bistripolyphosphate, dysprosium(III) triethylenetetraaminehexaacetate and thulium(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonate (TmDOTP). Over the past decade, TmDOTP has become the reagent of choice for in vivo sodium NMR spectroscopy. It provides a good separation of the intracellular and extracellular sodium resonances and is well tolerated by animals. The use of TmDOTP as a hyperfine in vivo sodium NMR shift reagent provides a nondestructive method for the observation of intracellular sodium levels. Viable cells maintain a 10 to 20-forld concentration gradient between the intracellular and extracellular sodium. Levels of sodium play an important role in cellular function through the regulation intracellular pH and intracellular calcium levels. Any deviation from this gradient is an indication of detrimental processes. TmDOTP has been used to study sodium levels in normal and ischemic heart, brain , kidney, liver and neoplastic human tissues.