title: Decorporation of systemically distributed americium by a novel orally administered diethylenetriaminepentaacetic acid (DTPA) formulation in beagle dogs.
abstract: Novel decorporation agents are being developed to protect against radiological accidents and terrorists attacks. Radioactive americium is a significant component of nuclear fallout. Removal of large radioactive materials, such as 241Am, from exposed persons is a subject of significant interest due to the hazards they pose. The objective of this study was to evaluate the dose-related efficacy of daily doses of NanoDTPA™ Capsules for decorporating Am administered intravenously as a soluble citrate complex to male and female beagle dogs. In addition, the efficacy of the NanoDTPA™ Capsules for decorporating 241Am was directly compared to intravenously administered saline and DTPA. Animals received a single IV administration of 241Am(III)-citrate on Day 0. One day after radionuclide administration, one of four different doses of NanoDTPA™ Capsules [1, 2, or 6 capsules d(-1) (30 mg, 60 mg, or 180 mg DTPA) or 2 capsules BID], IV Zn-DTPA (5 mg kg(-1) pentetate zinc trisodium) as a positive control, or IV saline as a placebo were administered. NanoDTPA™ Capsules, IV Zn-DTPA, or IV saline was administered on study days 1-14. Animals were euthanized on day 21. A full necropsy was conducted, and liver, spleen, kidneys, lungs and trachea, tracheobronchial lymph nodes (TBLN), muscle samples (right and left quadriceps), gastrointestinal (GI) tract (stomach plus esophagus, upper and lower intestine), gonads, two femurs, lumbar vertebrae (L1-L4), and all other soft tissue remains were collected. Urinary and fecal excretion profiles were increased approximately 10-fold compared to those for untreated animals. Tissue contents were decreased compared to untreated controls. In particular, liver content was decreased by approximately eightfold compared to untreated animals. The results from this study further demonstrate that oral NanoDTPA™ Capsules are equally efficient compared to IV Zn-DTPA in decorporation of actinides.
authors: *Nanotherapeutics, Inc., Alachua, FL 32615; †Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM.
authors: James P
authors: JP
authors: Wilson
authors: Ronald R
authors: RR
authors: Cobb
authors: Nathanael W
authors: NW
authors: Dungan
authors: Laura L
authors: LL
authors: Matthews
authors: Bärbel
authors: B
authors: Eppler
authors: Kenneth V
authors: KV
authors: Aiello
authors: Shiro
authors: S
authors: Curtis
authors: Teannetta
authors: T
authors: Boger
authors: Raymond A
authors: RA
authors: Guilmette
authors: Waylon
authors: W
authors: Weber
authors: Melanie
authors: M
authors: Doyle-Eisele
authors: James D
authors: JD
authors: Talton
mesh_terms: D000284:Administration, Oral; D000576:Americium / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003666:Decontamination / Q000379:methods*; D004285:Dogs; D005260:Female; D008297:Male; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D002614:Chelating Agents; C060068:diethylenetriaminetetraacetic acid; D004369:Pentetic Acid; D000576:Americium