The favorable nuclear properties of actinium-225 (Ac-225) have led to propo
sal of this isotope for use in radioimmunotherapy. In an effort to reduce t
he toxicity of free Ac-225, a series of ligands were evaluated for stabilit
y in vivo. Loss of Ac-225 from acyclic chelating agents resulted in high li
ver uptake and poor whole body clearance. The macrocyclic ligands c-DOTA, P
EPA, and HEHA were evaluated, and Ac-225-HEHA showed exceptional stability
in vivo. Ac-225 chelated with EDTA, DTPA, DOTA, or PEPA permitted substanti
al accumulation of the radionuclide to the Liver, while the Ac-225-HEHA com
plex was essentially excreted within minutes of administration. The prepara
tion of the ligands and radiolabeled complexes and the biodistribution resu
lts will be discussed.