PHARMACEUTICAL PROPERTIES, BIODISTRIBUTION, AND IMAGING CHARACTERISTICS OF MANGANESE-MESOPORPHYRIN - A POTENTIAL HEPATOBILIARY CONTRAST AGENT FOR MAGNETIC-RESONANCE-IMAGING

OBJECTIVES. Manganese (III) mesoporphyrin (Mn-mesoporphyrin) was inves tigated for its pharmaceutical properties and magnetic resonance imagi ng characteristics as a potential hepatobiliary contrast agent. METHOD S. Solubility, partition coefficient, plasma binding, proton relaxatio n enhancement, biodistribution, biliary excretion, liver extraction ra tio, and liver enhancement were measured in various in-vitro and in-vi vo systems. RESULTS. Mn-mesoporphyrin was soluble and stable at modera te alkaline pH in phosphate buffer. The octanol/water coefficient was 25.98, and the compound was highly protein bound. R1 for water and pla sma were 1.94 and 2.35 L/mmol sec, respectively. R1 in liver was calcu lated to be 15.72 L/mmol sec. Biodistribution studies in rats and mice confirmed hepatotrophic properties and biliary excretion was 65 % ove r 24 hours. First pass liver uptake was 15 %. Magnetic resonance imagi ng studies showed persistent liver enhancement at 0.05 mmol/kg. CONCLU SION. Mn-mesoporphyrin is a lipophilic compound that shows potential a s a hepatobiliary magnetic resonance contrast agent.