TmDOTP5- as a 23Na shift reagent for the in vivo rat kidney

Since transmembrane sodium gradient is essential to many cell functions, there is continuing interest in methods that differentiate intracellular and extracellular Na+. In the kidney, shift reagent (SR) aided 23Na magnetic resonance spectroscopy (MRS) has been successfully used only in isolated cells, tubules, and the perfused organ. In this report, we demonstrate for the first time that TmDOTP5- can be used to distinguish Na+ compartments in kidneys in vivo. Infusion of 80 mM TmDOTP5- without added Ca2+ produced three resolved 23Na resonances, which we have assigned to intracellular Na+, vascular Na+, and intraluminal Na+. In comparison, infusion of 400 mM DyTTHA3- produced two broad and unresolved resonances. The 31P spectra of the cellular high energy phosphate metabolites indicate that TmDOTP5- is safe for in vivo applications. Washout studies suggest that this SR displays renal clearance similar to that of MR imaging contrast agents. However, the glomerular filtration rate (GFR) in animals infused with TmDOTP5- was reduced by 49% compared with the GFR in control animals, perhaps due to the hypotensive effects of the SR. We conclude that TmDOTP5- is effectively cleared from the blood of live animals but that a different formulation will be required for clinical application.