title: Magnetic resonance imaging-histomorphologic correlation studies on paramagnetic metalloporphyrins in rat models of necrosis.
abstract: OBJECTIVE
  The authors intended to confirm previous findings that paramagnetic porphyrins are avid only for intratumoral nonviable tissues, but not for viable tumor cells, and to test the hypothesis that necrosis, regardless of location and origin, can be visualized by metalloporphyrin enhanced magnetic resonance imaging (MRI).
  
  
  METHODS
  Intravenous administrations of gadolinium mesoporphyrin (Gd-MP), manganese tetraphenylporphyrin (Mn-TPP), manganese methylpyrroporphyrin-gadopentetate dimeglumine complex (Mn-MPP-Gd) and manganese tetra(4-sulfonatophenyl)porphyrin (MnTPPS4) at 0.05 mmol/kg were compared with those of gadopentetate dimeglumine (Gd-DTPA) at 0.1 mmol/kg in 38 rats with cholestatic liver necrosis, alcohol- and laser-induced coagulation necrosis in liver, and skeletal muscle, reperfused hepatic infarction, and segmental renal infarction. T1-weighted spin echo MRI (TR/TE = 300/15 mseconds) was acquired before and as long as 48 hours after injection, matched with histologic findings, and correlated with Gd/ Mn tissue content measurements.
  
  
  RESULTS
  Both Gd-DTPA and the four metalloporphyrins initially caused a similar nonspecific negative contrast enhancement in the necrosis. However, a strong and persisting positive enhancement (necrosis-to-normal contrast ratio ranging from 1.5 to 2.0) developed only with metalloporphyrins in all types of necrosis. In liver and kidney, Gd and Mn concentrations at 24 hours were comparable in necrotic and normal tissues. In muscle, the concentrations were more than eight times higher in necrotic than in normal tissue.
  
  
  CONCLUSIONS
  The implied affinity of metalloporphyrins for necrosis with presumably increased relaxivity suggests a possible mode of targetability for MRI contrast media that may elicit novel applications.
authors.affiliation: Department of Radiology, University Hospitals, K.U. Leuven, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Ni
authors.forename: C
authors.initials: C
authors.lastname: Petré
authors.forename: Y
authors.initials: Y
authors.lastname: Miao
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: E
authors.initials: E
authors.lastname: Cresens
authors.forename: P
authors.initials: P
authors.lastname: Adriaens
authors.forename: H
authors.initials: H
authors.lastname: Bosmans
authors.forename: W
authors.initials: W
authors.lastname: Semmler
authors.forename: A L
authors.initials: AL
authors.lastname: Baert
authors.forename: G
authors.initials: G
authors.lastname: Marchal
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000493:pharmacokinetics; D007089:Image Enhancement / Q000379:methods; D007238:Infarction / Q000175:diagnosis / Q000378:metabolism; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D008665:Metalloporphyrins; D019786:Gadolinium DTPA