Efficacy of a Novel Orally Administered Formulation of DTPA Tablets for Decorporating an Intravenously Injected Radionuclide: A Comparison with Intravenously Administered Licensed DTPA

Abstract

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.