PHOSPHONATE-MODIFIED GDDTPA COMPLEXES .2. EVALUATION IN A RAT MYOCARDIAL INFARCT MODEL

The localization of 1-hydroxy-3-aminopropane-1,1-diphosphonate-modified GdDTPA (GdDTPA-HPDP) and 4-aminobutane-1,1-diphosphonate-modified GdDTPA (GdDTPA-BDP) in (1) normal and (2) infarcted rat hearts has been measured. The phosphonate-modified agents are preferentially retained in infarcted myocardium. The ratio of GdDTPA-HPDP accumulated in whole infarcted heart to that detected in normal heart is 15 at 2 hours after injecting a dose of 50 to 100-mu-mol/kg; the ratio is 2 for GdDTPA. At these doses, significant changes are detected in the tissue relaxation rates. An average relaxivity of 11.2 (mmol-sec)-1 is calculated for the agent in the infarcted whole heart. GdDTPA-BDP, in comparison, displayed prolonged blood retention. The result is a low diseased-to-normal heart ratio (approximately 2) at 2 hours, making this agent less attractive as a contrast agent.