Synthesis of 99mTc(CO)3‐mebrofenin via [99mTc(OH2)3(CO)3]+ precursor and comparative pharmacokinetics studies with 99mTc‐mebrofenin

The organometallic precursor fac‐[^99mTc(OH₂)₃(CO)₃]⁺ was reacted with trimethyl‐bromoacetanilido‐iminodiacetic acid (mebrofenin) in phosphate buffered saline (pH 7) at 70°C for 1 h to produce the complex, ^99mTc(CO)₃‐mebrofenin, in >95% yields. High performance liquid chromatography analysis indicated the formation of a single species. In vitro studies of ^99mTc(CO)₃‐mebrofenin showed that the complex is stable for 24 h. No decomposition or alteration of the complex was observed in the presence of excess amount of cysteine and histidine. ^99mTc‐mebrofenin was also prepared for comparative evaluation by the conventional method using a ready to use kit HPLC analysis of this complex showed presence of two species. Biodistribution studies in normal Swiss mice with ^99mTc(CO)₃‐mebrofenin showed hepatobiliary clearance. However, the retention in liver was higher (13% at 1 h p.i.) as compared to that of ^99mTc‐mebrofenin (3.4% at 1 h p.i.). Copyright © 2003 John Wiley & Sons, Ltd.