title: Improved in vivo stability of actinium-225 macrocyclic complexes.
abstract: 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.
authors.affiliation: National Cancer Institute, National Institutes of Health, Building 10, Room B3B69, Bethesda, Maryland 20892, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Deal
authors.forename: I A
authors.initials: IA
authors.lastname: Davis
authors.forename: S
authors.initials: S
authors.lastname: Mirzadeh
authors.forename: S J
authors.initials: SJ
authors.lastname: Kennel
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000186:Actinium; D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000085:Acetates; D002614:Chelating Agents; D008024:Ligands; D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C120798:actinium 1,4,7,10,13,16-hexaazacyclohexadecane-N,N',N'',N''',N'''',N'''''-hexaacetic acid; D000186:Actinium