Synthesis and biological evaluation of Tc-99m N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate: a potential replacement for [131I]o-iodohippurate

Abstract

A new technetium-chelating agent based on amide and mercaptide donor groups, N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate, was synthesized as an analog of previously described N,N'-bis(mercaptoacetyl)ethylenediamine (DADS). Complexation of Tc-99m with the new chelating group resulted in two components that were separable by high-performance liquid chromatography. The component that eluted first demonstrated high specificity for renal excretion, with over 90% in the urine of rabbits at 35 min, 87% in the urine of mice at 2 hr, and 1.6% or less in the intestines of mice. Excretion was rapid, with the first component equaling or exceeding [131I]o-iodohippurate in the urine of rabbits at all times. The second or latter component demonstrated comparable specificity but slightly slower renal excretion kinetics. Clinical trials with the first component are probably warranted.