title: Paramagnetic metalloporphyrins: infarct avid contrast agents for diagnosis of acute myocardial infarction by MRI.
abstract: In previous experiments in tumors we demonstrated that metalloporphyrins are particularly avid for nonviable tumor components. This study was performed to find out whether these agents can be used as MRI contrast agents for the visualization of acute myocardial infarction (MI). A total of 44 rats, 6 normal controls and 38 with occlusive MI (2-24 h old), were used. Gadolinium mesoporphyrin (Gd-MP) or manganese tetraphenylporphyrin (Mn-TPP) was intravenously injected at doses of 0.1, 0.05, and 0.01 mmol/kg. Three to 24 h after injection, axial and coronal T1-weighted (TR/TE 300/15 ms) spin-echo MR images were obtained before and after killing the animals and correlated with triphenyl tetrazolium chloride (TTC) histochemical preparations. The Gd-MP content in infarcted and noninfarcted myocardium was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). MRI without contrast media could not discern the MI. However, 3-24 h after injection of either Gd-MP or Mn-TPP, the infarcted area was positively stained on MR images. This area matched well with the negatively TTC-stained area on the heart slices (r = 0.97). The contrast ratios between the infarcted necrotic myocardium and the noninfarcted regions varied from 150 to 300% depending on the type of agents and doses used. Neither false-positive nor false-negative findings were encountered. The metalloporphyrin concentration was more than 10 times higher in the infarcted than in the noninfarcted heart. Metalloporphyrins appear to be promising MRI contrast agents for detection and quantification of necrosis in MI. These preclinical results may open new perspectives in cardiac imaging.
authors.affiliation: Department of Radiology, University Hospitals K.U. Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Marchal
authors.forename: Y
authors.initials: Y
authors.lastname: Ni
authors.forename: P
authors.initials: P
authors.lastname: Herijgers
authors.forename: W
authors.initials: W
authors.lastname: Flameng
authors.forename: C
authors.initials: C
authors.lastname: Petré
authors.forename: H
authors.initials: H
authors.lastname: Bosmans
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: W
authors.initials: W
authors.lastname: Ebert
authors.forename: C S
authors.initials: CS
authors.lastname: Hilger
authors.forename: D
authors.initials: D
authors.lastname: Pfefferer
authors.forename: W
authors.initials: W
authors.lastname: Semmler
authors.forename: A L
authors.initials: AL
authors.lastname: Baert
mesh_terms: D000818:Animals; D004396:Coloring Agents; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy; D005682:Gadolinium / Q000008:administration & dosage / Q000493:pharmacokinetics; D006651:Histocytochemistry; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods; D008345:Manganese / Q000008:administration & dosage / Q000493:pharmacokinetics; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D013057:Spectrum Analysis; D013778:Tetrazolium Salts
chemical_list: D004396:Coloring Agents; D003287:Contrast Media; D008652:Mesoporphyrins; D008665:Metalloporphyrins; D013778:Tetrazolium Salts; C041471:manganese tetraphenylporphyrin; D008345:Manganese; C009591:triphenyltetrazolium; D005682:Gadolinium