Fe(III)-EHPG and Fe(III)-5-Br-EHPG as contrast agents in MRI: an animal study

The development of specific agents for hepatobiliary magnetic resonance imaging (MRI), iron (III) ethylenebis-(2-hydroxyphenylglycinate) [Fe(EHPG)-] and its derivative iron (III)-N, N' ethylenebis[5-bromo-2-hydroxyphenyl)-glycinate] [Fe(5-Br-EHPG)-] was investigated. Test procedures included method of synthesis, identification, and a test for purity, lipophilicity, toxicity, relaxivity, biodistribution and animal MRIs. Free EHPG and free Fe3+ were undetectable in the purity test. The partition coefficient for the lipophilicity of Fe(EHPG)- was 0.007 and for Fe(5-Br-EHPG)- it was 1.785. The acute toxicity test of Fe(EHPG)- in mice revealed that the LD50 dose of Fe(EHPG)- was 8 mmol/kg. Their relaxivity values were 1.167 and 0.780 s-1mM-1 in an agarose gel system and 1.313 and 0.725 s-1mM-1 in an aqueous solution, respectively. Biodistribution was performed with 59Fe(EHPG)- in anesthetized dogs. There was 1.097% to 1.19% contrast excretion through the opened common bile duct and 54.29% to 61.45% through the urinary tract in a six-hour period. After six hours, the residual contrast agent was only evident in the kidney and liver. The MRIs of dogs with intravenous contrast administration showed significant opacification of the common bile duct within a 10-minute period. Complete opacification of the biliary system could be identified within 1.5 hours. There was no significant difference in the enhancement effect between the inversion recovery sequence and T1-weighted spin echo sequence. The change in signal intensity of the hepatobiliary system on MRIs was similar between Fe(EHPG)- and Fe(5-Br-EHPG)-. The recommended administration dose was 0.083 mmol/kg for both contrast agents.(ABSTRACT TRUNCATED AT 250 WORDS)