MACROMOLECULAR INFARCT-SPECIFIC MAGNETIC-RESONANCE CONTRAST AGENTS

PURPOSE. TO identify safe and effective magnetic resonance imaging (MR I) agents for infarction, the authors investigate the possibility of u sing a small population of infarct-avid phosphonates to target macromo lecular MRI agents to infarction. METHODS. Several phosphonylated radi olabeled (gadolinium-153, iron-59) macroaggregates were synthesized. B iodistribution was assessed in a drug-induced rat model of diffuse myo cardial infarction (MI). Agents that demonstrated preferential accumul ation in infarcted whole hearts were additionally evaluated in occlude d and reperfused rabbit hearts. Phosphonylated T2 agents have been tho roughly studied with MRI of MI, and the results are reported. RESULTS AND DISCUSSION. Typically, core size was 11 to 13 nm and particle size was 120 nm. Phosphorus content was <12% by weight. The relaxivities w ere R1 of 12 to 20 1/(mM sec) and R2 of 119 to 270 1/(mM sec) at 20 MH z in .5% agar. One hour after injection of .03 mmol/kg of the agent in to six rabbits (45-minute occlusion with 1-hour reperfusion), the aver age myocardial tissue agent content was 70 +/- 30 nmol Fe/g (infarct) compared with 9 +/- 2 nmolFe/g (normal); P = .000. Similarly, the infa rct zone was clearly discerned by MRI as hypointense on spin echo imag es, TR/TE = 400/30 msec and 2,000/30 msec with low-dose agent, whereas infarct was barely discernible only on TR/TE = 2,000/90 msec without agent. The magnetic resonance infarcts correlated with histology. CONC LUSION. Simple phosphonylated macromolecules can be used as low-dose, infarct-specific MRT agents.