Comparison of (225) actinium chelates: Tissue distribution and radiotoxicity

The biodistribution and tissue toxicity of intravenously administered 225-a ctinium (Ac-225) complexed with acetate, ethylene diamine tetraacetic acid (EDTA), 1, 4, 7, 10, 13-pentaazacyclopentadecane-N, N', N ", N''', N''''-pe ntaacetic acid (PEPA), or the "a" isomer of cyclohexyl diethylenetriamine p entaacetic acid (CHX-DTPA), were examined. The percent of injected dose per organ and per gram of tissue for each chelate complex was determined. Ac-2 25-CHX-DTPA was evaluated further for radiotoxic effects. Mice receiving gr eater than or equal to 185 kBq Ac-225-CHX-DTPA suffered 100% morbidity by 5 days and 100% mortality by 8 days postinjection, and all animals evaluated had significant organ damage. The in vivo instability of the Ac-225-CHX-DT PA complex likely allowed accumulation of free Ac-225 in organs, which resu lted in tissue (C) 1999 Elsevier Science Inc. All rights reserved. patholog y.