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 deleterious effects on heart rate, blood pressure, left ventricular force and AV conductance in ferret hearts in vivo at the magnetic resonance imaging (MRI)-effective dose of 0.05 mmol/kg body weight. In MRI images, a 1H signal intensity enhancement is observed in the following organs in decreasing order of the effect: heart approximately spleen > kidney > liver. This enhancement is stable for over 3 h in all organs. The results of 1H MRI and electron micrographs indicate that the lipophilic fatty acyl groups in the ligand BME structure and the particle sizes of liposomal Gd(BME-DTTA) are two important factors for tissue specificity 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 decrease in relaxivity was observed in a sample stored at room temperature, most likely reflecting some deterioration in liposome chemistry.
Chu
W J
WJ
Department of Medicine, University of Alabama at Birmingham 35294, USA.
Simor
T
T
Elgavish
G A
GA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003080:Cold Temperature; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D004562:Electrocardiography / Q000187:drug effects; D005289:Ferrets; D019786:Gadolinium DTPA; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007928:Lethal Dose 50; D008081:Liposomes; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism*; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution; D016277:Ventricular Function, Left / Q000187:drug effects
D003287:Contrast Media; D008081:Liposomes; C073487:N(3),N(6)-bis(2'-myristoyloxyethyl)-1,8-dioxotriethylenetetramine-N,N,N',N'-tetraacetic acid; D004369:Pentetic Acid; D019786:Gadolinium DTPA