title: Comparison of 225actinium chelates: tissue distribution and radiotoxicity.
abstract: The biodistribution and tissue toxicity of intravenously administered 225-actinium (225Ac) complexed with acetate, ethylene diamine tetraacetic acid (EDTA), 1, 4, 7, 10, 13-pentaazacyclopentadecane-N, N', N", N"', N""-pentaacetic acid (PEPA), or the "a" isomer of cyclohexyl diethylenetriamine pentaacetic acid (CHX-DTPA), were examined. The percent of injected dose per organ and per gram of tissue for each chelate complex was determined. 225Ac-CHX-DTPA was evaluated further for radiotoxic effects. Mice receiving > or =185 kBq 225Ac-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 225Ac-CHX-DTPA complex likely allowed accumulation of free 225Ac in organs, which resulted in tissue pathology.
authors.affiliation: Life Sciences Division, Oak Ridge National Laboratory, Tennessee 37831-6101, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Davis
authors.forename: K A
authors.initials: KA
authors.lastname: Glowienka
authors.forename: R A
authors.initials: RA
authors.lastname: Boll
authors.forename: K A
authors.initials: KA
authors.lastname: Deal
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: M
authors.initials: M
authors.lastname: Stabin
authors.forename: P N
authors.initials: PN
authors.lastname: Bochsler
authors.forename: S
authors.initials: S
authors.lastname: Mirzadeh
authors.forename: S J
authors.initials: SJ
authors.lastname: Kennel
mesh_terms: D000186:Actinium / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D004307:Dose-Response Relationship, Radiation; D005260:Female; D017879:Isothiocyanates / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D017879:Isothiocyanates; C085678:N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid; D004369:Pentetic Acid; D000186:Actinium