title: Pharmaceutical properties, biodistribution, and imaging characteristics of manganese-mesoporphyrin. A potential hepatobiliary contrast agent for magnetic resonance imaging.
abstract: OBJECTIVE
  Manganese (III) mesoporphyrin (Mn-mesoporphyrin) was investigated for its pharmaceutical properties and magnetic resonance imaging characteristics as a potential hepatobiliary contrast agent.
  
  
  METHODS
  Solubility, partition coefficient, plasma binding, proton relaxation enhancement, biodistribution, biliary excretion, liver extraction ratio, and liver enhancement were measured in various in-vitro and in-vivo systems.
  
  
  RESULTS
  Mn-mesoporphyrin was soluble and stable at moderate alkaline pH in phosphate buffer. The octanol/water coefficient was 25.98, and the compound was highly protein bound. R1 for water and plasma were 1.94 and 2.35 L/mmol sec, respectively. R1 in liver was calculated to be 15.72 L/mmol sec. Biodistribution studies in rats and mice confirmed hepatotrophic properties and biliary excretion was 65% over 24 hours. First pass liver uptake was 15%. Magnetic resonance imaging studies showed persistent liver enhancement at 0.05 mmol/kg.
  
  
  CONCLUSIONS
  Mn-mesoporphyrin is a lipophilic compound that shows potential as a hepatobiliary magnetic resonance contrast agent.
authors.affiliation: Department of Radiology, University of Washington School of Medicine, Seattle 98195.
authors.forename: U P
authors.initials: UP
authors.lastname: Schmiedl
authors.forename: J A
authors.initials: JA
authors.lastname: Nelson
authors.forename: D H
authors.initials: DH
authors.lastname: Robinson
authors.forename: A
authors.initials: A
authors.lastname: Michalson
authors.forename: F
authors.initials: F
authors.lastname: Starr
authors.forename: T
authors.initials: T
authors.lastname: Frenzel
authors.forename: W
authors.initials: W
authors.lastname: Ebert
authors.forename: G
authors.initials: G
authors.lastname: Schuhmann-Giampieri
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000033:anatomy & histology; D003110:Colonic Neoplasms / Q000378:metabolism; D003287:Contrast Media; D005260:Female; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008652:Mesoporphyrins / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D008652:Mesoporphyrins; C067090:manganese mesoporphyrin