1999/07/01 by Kim A. Deal, Ila A. Davis, Saed Mirzadeh +2 · 5 citations
Medicine · Chemistry · #Radiopharmaceutical Chemistry and Applications #Peptidase Inhibition and Analysis #Synthesis and Biological Evaluation
paper · doi:10.1021/jm990141f
openalex publication_date 1999/07/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/27
The favorable nuclear properties of actinium-225 ((225)Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free (225)Ac, a series of ligands were evaluated for stability in vivo. Loss of (225)Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c-DOTA, PEPA, and HEHA were evaluated, and (225)Ac-HEHA showed exceptional stability in vivo. (225)Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the (225)Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.