IN-VIVO CHARACTERIZATION OF GD(BME-DTTA), A MYOCARDIAL MRI CONTRAST AGENT - TISSUE DISTRIBUTION OF ITS MRI INTENSITY ENHANCEMENT, AND ITS EFFECT ON HEART FUNCTION

We have determined an LD50 of 0.56+/-0.05 mmol/kg for liposomal Gd(BME -DTTA) in mice and also shown that liposomal Gd(BME-DTTA) has no delet erious effects on heart rate, blood pressure, left ventricular force a nd AV conductance in ferret hearts in vivo at the magnetic resonance i maging (MRT)-effective dose of 0.05 mmol/kg body weight, In MRI images , a H-1 signal intensity enhancement is observed in the following orga ns in decreasing order of the effect: heart approximate to spleen>kidn ey>liver. This enhancement is stable for over 3 h in all organs, The r esults of H-1 MRT and electron micrographs indicate that the lipophili c fatty acyl groups In the ligand BME structure and the particle sizes of liposomal Gd(BME-DTTA) are two important factors for tissue specif icity of liposomal Gd(BME-DTTA) in the intensity enhancement, In vitro relaxivity of a liposomal Gd(BME-DTTA) sample, stored at 4 degrees C, remained stable for over 4 months of observation, but a significant d ecrease in relaxivity was observed in a sample stored at room temperat ure, most likely reflecting some deterioration in liposome chemistry, (C) 1997 by John Wiley & Sons, Ltd.