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.

Abstract

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.

• Authors: W J Chu, T Simor, G A Elgavish
• Journal: NMR in biomedicine (NMR Biomed) Vol. 10 Issue 2 Pg. 87-92 (Apr 1997) ISSN: 0952-3480 [Print] England
• PMID: 9267866 (Publication Type: Journal Article)

Chemical References

• Contrast Media
• Liposomes
• N(3),N(6)-bis(2'-myristoyloxyethyl)-1,8-dioxotriethylenetetramine-N,N,N',N'-tetraacetic acid
• Pentetic Acid
• Gadolinium DTPA

Topics

• Animals
• Blood Pressure (drug effects)
• Cold Temperature
• Contrast Media (administration & dosage, pharmacokinetics, toxicity)
• Electrocardiography (drug effects)
• Ferrets
• Gadolinium DTPA
• Heart (anatomy & histology, drug effects)
• Heart Rate (drug effects)
• Lethal Dose 50
• Liposomes
• Magnetic Resonance Imaging (methods)
• Male
• Mice
• Mice, Inbred ICR
• Myocardium (metabolism)
• Pentetic Acid (administration & dosage, analogs & derivatives, pharmacokinetics, toxicity)
• Tissue Distribution
• Ventricular Function, Left (drug effects)