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

Synthesis and in Vivo Evaluation of New Contrast Agents for Cardiac MRI

“…10 An LD 50 of 0.56 mmol/kg for liposomal Gd(BME-DTTA) has been published. 25 The LD 50 values for the Gd complexes of other BME analogue complexes were in the same range, i.e., ∼0.6 mmol/kg, as we expected, based on the relative similarity of their stability constants. 22,23 The LD 50 of the ligands should be similar to this ∼0.6 mmol/kg range.…”

“…GdCl 3 , however, cannot be injected intravenously due to its insolubility at physiological pH and to its high affinity for the calcium-binding sites of a living being, owing to its greater charge/radius ratio . An LD 50 of 0.56 mmol/kg for liposomal Gd(BME-DTTA) has been published . The LD 50 values for the Gd complexes of other BME analogue complexes were in the same range, i.e., ∼0.6 mmol/kg, as we expected, based on the relative similarity of their stability constants. , The LD 50 of the ligands should be similar to this ∼0.6 mmol/kg range.…”

“…To examine the effect of our contrast agent on heart function, the heart rate and blood pressure was continuously monitored before and after any contrast agent injected. During our recent MRI experiments and in our previous studies, 24,25 the heart rate of the ferrets remained within the 210-240 beats/min range, and systolic and diastolic pressures remained within the ranges of 210-225 and 160-170 mmHg, respectively.…”

“…The myocardial specificity of liposomal Gd(BME-DTTA) was already observed in our previous ferret experiments. 24,25 It is our experience that the gadolinium complexes of BME-DTTA and its analogues induce the highest IE in the heart among all organs. It is our hypothesis that this myocardial specificity results from the fatty acid chain of our compounds.…”

“…The formation of a discoidal structure could be explained by the tendency of the long myristoyl chains of the BME-DTTA ligand to associate with the outer surface of the disk formed by the phosphatidylcholine. 25 The surfactant molecule, cholesterol, was used during the preparation of liposomal Gd(BME-DTTA) to prevent the fusion of small sonicated liposomes. 27 Such fusion, if occurred, would decrease the surface-to-volume ratio of the vesicles resulting in a reduction in relaxivity.…”