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Gadolinium complexes have two advantages: their toxicity is very low and the paramagnetic properties are adequate enough to give a useful signal with magnetic resonance imaging (MRI). The effects of several MRI contrast media on the activity of two brain enzymes, glutamate decarboxylase (GAD) and cholineacetyl transferase (ChAT), were investigated. The study was performed on homogenates of rat striatum with variable concentrations of gadolinium sulphate, EDTA, DTPA, DOTA, Gd-EDTA, Gd-DTPA and Gd-DOTA (from 10(-2) mol/l to 10(-9) mol/l. Gadolinium in its ionic form and the chelators of cation agents such as EDTA, DTPA and DOTA inhibit GAD, a calcium dependent enzyme, whereas they have no inhibiting effect on the activity of ChAT, a calcium independent enzyme. Gadolinium complexes inhibit the GAD activity by about 15 per cent whereas they do not modify that of ChAT. The complex form of gadolinium has the advantage of retaining its paramagnetism while drastically lowering its toxicity.

We examined the use of isotonic and hypertonic contrast media injected intravenously in the dog from the standpoint of cardiovascular tolerance after right atrial injections performed at 2.56 and 5.12 g I/second. The parameters measured were lead II of the electrocardiograph, heart rate, pulmonary and abdominal arterial pressure, and aortic flow. Three contrast media, ioxitalamate, ioxaglate, and iopamidol (two ionic and one nonionic), were compared, either concentrated (32% iodine) or dilute and isotonic with plasma (ioxaglate 160 mg I/mL and iopamidol 128 mg I/mL). At an injection rate of 5.12 g I/second, iopamidol-128 showed lower electrophysiologic tolerability and caused a higher increase in aortic flow than ioxitalamate 160 or ioxaglate 160. These effects may explain the lower radiographic efficacy observed with iopamidol-128 in previous digital subtraction angiography studies.

The complex (Gd-DOTA) meglumine has recently been used as an MRI contrast agent in humans. Due to its particularly interesting physicochemical properties, the risk of in vivo dissociation of the complex is reduced. Indeed, as a result of the macrocyclic nature of the DOTA ligand, Gd-DOTA appears very stable, demonstrating a calculated conditional stability constant of 10(22.19) at pH = 7. Other characteristics making Gd-DOTA a positively attractive compound include slow dissociation kinetics inherent in the rigidity of the macrocycle and marked specific affinity of DOTA for gadolinium in comparison with other endogenous ions. Finally, although the relaxivity R1 of Gd-DOTA at 20 MHz appears similar to that of Gd-DTPA, Gd-DOTA demonstrates higher paramagnetic efficacy at low field strength due to greater symmetry of the complex. Such promising properties open up wide prospects for the use of Gd-DOTA in MRI.