SEARCH

SEARCH BY CITATION

Keywords:

  •  ;
  • decorporation;
  • chelation;
  • DTPA;
  • radionuclide;
  • 241Am;
  • countermeasures

Abstract

Strategy, Management and Health Policy
Enabling Tchnology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Durg Delivery, PharmacokineticsClinical Development Phases I-III Regulatory, Quality, ManufacturingPostmarketing Phase IV

A proprietary minitablet formulation of the chelating agent diethylenetriaminepentaacetic acid (DTPAMT) was administered orally to rats injected with (241 Am) (III)-citrate and compared with untreated controls. The positive control was intravenously administered diethylenetriaminepentaacetate (DTPA) (IVDTPA). Groups of six young adult rats (three male, three female) were injected intravenously with 241 Am, with each rat placed in an individual metabolism cage for excreta collection. The groups were then treated once with IVDTPA or DTPAMT at 1 h, or 1, 5, or 14 days postinjection, with sacrifice at 8, 8, 12, and 21 days postinjection, respectively. Sacrifice of three untreated control groups occurred 8, 12, and 21 days postinjection. At necropsy, all tissues, associated urine, feces, and cage wash samples were collected and analyzed for (241 Am) content. The average recovery for all experimental groups was 95.2 ± 3.6% administered 241 Am dose. Tissue and excreta analyses of (241 Am) were compared for the treatment groups and untreated controls and with IVDTPA using two-way analysis of variance. DTPAMT 241 Am removal efficacy was statistically significant for all administration times compared with untreated controls. For systemically administered (241 Am), the primary deposition sites, bone and liver, incurred the highest radiation doses. DTPAMT reduced liver (241 Am) content by 60–70% and bone content by 40% at treatment times of 1 h,1 day, and 5 days when compared with untreated controls. For all times, DTPAMT compared well with IVDTPA. For DTPAMT, (241 Am) excretion elevation in urine was protracted beyond that typically observed with IVDTPA.