Phosphonate-modified Gd-DTPA complexes. III: The detection of myocardial infarction by MRI

The potential of a phosphonate-modified-Gd-DTPA for MR image enhancement of myocardial infarction has been demonstrated in imaging experiments on rats. The agent, 1-hydroxy-3-aminopropane-1,1-diphosphonate-modified-Gd-DTPA (Gd-DTPA-HPDP) accumulates in two models of myocardial infarction, (i.e., drug-induced diffusely infarcted whole hearts and in focal acute myocardial infarction from a left coronary artery ligation). The time course of the accumulation of the agent in the focal model of infarction and subsequent washout has also been followed in vitro. Results of this kinetics demonstrate that the agent first perfuses all normal fluid spaces and then slowly diffuses into the occluded zone where it is retained for a prolonged period, in sufficient quantities to be useful as an MRI contrast agent. Wash-out of the agent from normal myocardium is fast and complete with MR signal returning to background in minutes. The specificity of Gd-DTPA-HPDP for soft-tissue calcification and its retention within the infarcts permitted imaging at 1 to 2 h postinjection, (after unbound material has cleared the normal tissues). Infarcted tissue appeared as regions of increased signal intensity in T1-weighted images (> 200% enhancement), and correlated with histopathology. Unmodified Gd-DTPA was not retained under identical conditions. Gd-DTPA-HPDP permits a more accurate infarct delineation than is possible with the unmodified agent.