Water proton 1/T1 nuclear magnetic relaxation dispersion (NMRD) profiles were measured for a water-soluble gadolinium(III) texaphyrin (Gd-tex) complex as a function of temperature and in the presence and absence of 5% human serum albumin (HSA). Upon dissolving the complex in water (0.259 mM), the water relaxivity values decreased with time but remained higher than those of free GD3+(aq) at all fields. Concurrent measurements of free Gd3+ using metallochromic dyes indicated that demetallation of the texaphyrin did not occur over a period of several days at 37 degrees C. The high relaxivity values and shape of the NMRD profile of this complex may be ascribed to a combination of large water coordination number (q estimated at 3.5) and long tau R. Upon mixing an aqueous solution of the complex with 5% HSA, the low-field water relaxivity slightly decreased whereas the high-field relaxivity increased relative to the free complex in water, and the relaxivities became nearly independent of temperature. These observations indicate that water exchange between the inner coordination sphere of Gd-tex and bulk water becomes limiting in the presence of HSA.

Contrast Media↗

PubMedDate not supplied

Dynamic evaluation of the hepatic uptake and clearance of manganese-based MRI contrast agents: a 31P NMR study on the isolated and perfused rat liver.

This spectroscopic study compares the mechanisms of the hepatic uptake of manganese chloride (MnCl2) and manganese dipyridoxyl diphosphate (MnDPDP). Alterations of the phosphorus-31 (31P)-NMR spectrum of the intracellular adenosine 5'-triphosphate (ATP) are used to monitor the internalization of manganese by the isolated and perfused rat liver. Mn2+ delivered as MnCl2 in the perfusate rapidly enters the hepatocytes, where it strongly interacts with ATP, inducing a broadening of the 31P lines. The inhibition of the process by nifedipine confirms that manganese ions cross the cellular membrane at least partly through Ca2+ channels. MnDPDP induces weaker but still significant changes of the ATP spectrum. The inability of pyridoxine to compete for the uptake of manganese confirms that the vitamin B6 carrier is not involved in the internalization process of the paramagnetic complex. Finally, preincubation of MnDPDP with blood does not increase the extent of the dissociation. The alterations of the 31P spectrum of the liver subsequent to the administration of MnDPDP are attributable to a fraction of free Mn2+ released by the chelate and delivered to the hepatocytes.

Adenosine Triphosphate↗

PubMedDate not supplied

Synthesis, characterization, and relaxivity of two linear Gd(DTPA)-polymer conjugates.

Two linear polyamide conjugates of Gd(DTPA)2- were synthesized and characterized by high-resolution nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography (SEC). DTPA was copolymerized with two different diamines, 1,6-hexanediamine and trans-1,4-cyclohexanediamine, yielding the polymers DTPA-HMD and DTPA-CHD, with low polydispersity. Their molecular flexibility in solution was studied using 13C spin-lattice relaxation time measurements, indicating that the cyclohexanediamine linking moiety of the DTPA-HMD polymer is more rigid than that of DTPA-CHD. The influence of the flexibility of the linking functionalities on the relaxivity of the Gd3+-DTPA-polymer conjugates was studied by water nuclear magnetic relaxation dispersion (NMRD). The relaxivity of the Gd(DTPA-CHD) polymer was only slightly higher than that of the Gd(DTPA-HMD) polymer, and only two times higher than the usual values for small Gd-DTPA-like chelates. The low relaxivities obtained for both polymers, much lower than expected from the polymer apparent molecular weights, result from their substantial residual flexibility, and also from a too long, nonoptimal, value of the inner-sphere water exchange rate. These polymeric compounds are also cleared very quickly from the blood of rats, indicating that they are of limited value as blood pool contrast agents for MRA.

Animals↗