Paramagnetic Pyrophosphate

Ferric pyrophosphate (Fe-PyP) was investigated in an animal model of acute myocardial infarction for its potential to provide contrast enhancement of the peri-infarct zone using magnetic resonance (MR) imaging. Radiotracer studies compared the biodistribution of soluble 59Fe-PyP with 99mTc-PyP in excised tissue samples. Preferential localization of 59Fe-PyP in the peri-infarct zone was found to be similar to 99mTc-PyP. The ratio (percent dose/gram of tissue) at the edge of the infarct to normal tissue was 1.30 +/- 0.16 and 1.44 +/- 0.33 for 99mTc-PyP and 59Fe-PyP, respectively. In initial studies with high doses of the contrast agent, gated T1-weighted MR images of animals with 48-hour-old infarcts were obtained at 15-minute intervals after injection of Fe-PyP at a dose of 350 mg/kg. Contrast enhancement of the infarct zone was observed in all studies and was maximal 15-30 minutes after injection. Signal intensity ratios (infarct/normal) increased from a baseline 1.31 +/- 0.22 to a peak 1.90 +/- 0.57. Studies were then performed with smaller amounts of Fe-PyP. Images obtained with 50 mg/kg Fe-PyP showed contrast enhancement beginning at 60 minutes. Toxicology studies showed primarily respiratory effects, which became significant at doses of 190 mg/kg. These preliminary studies suggest that Fe-PyP potentially could serve as an MR contrast agent to localize and size acute myocardial infarcts; however, its clinical use may be limited by potential toxicity and dose limitations.