DTPA Treatment of Wound Contamination in Rats with Americium: Evaluation of Urinary Profiles Using STATBIODIS Shows Importance of Prompt Administration

Abstract

INTRODUCTION:In the nuclear industry wound contamination with americium is expected to increase with decommissioning and waste management. Treatment of workers with diethylenetriaminepentaacetic acid (DTPA) requires optimization to reduce internal contamination and radiation exposure. OBJECTIVES:To evaluate and compare different DTPA protocol efficacies after wound contamination of rats with americium. METHODS:Wound contamination was simulated in rats by depositing americium nitrate in an incision in the hind limb. Different routes, times and frequencies of DTPA administration were evaluated. Individual daily urinary americium excretion and tissue retention were analyzed using the statistical tool STATBIODIS. Urinary profiles, urinary enhancement factors and inhibition percentages of tissue retention were calculated. RESULTS:A single DTPA administration the day of contamination induced a rapid increase in americium urinary excretion that decreased exponentially over seven days indicating that the first DTPA administration should be delivered early as possible. DTPA treatment limited americium uptake in systemic tissues irrespective of the protocol. Liver and skeleton burdens were markedly reduced which would drive reduction of radiation dose. Local or intravenous injections were equally effective.Inherent difficulties in wound site activity measurements did not allow identification of a significant decorporating effect at the wound site. Repeated intravenous injections of DTPA also increased americium urinary excretion which supports the use of multiple DTPA administrations shortly after wound contamination. CONCLUSION:Results from these statistical analyses will contribute to a better understanding of americium behavior in the presence or absence of DTPA, and may aid optimization of treatment for workers.

Four-decade follow-up of a plutonium-contaminated puncture wound treated with Ca-DTPA

“…Extensive chelation treatment may have also contributed to redistribution of activity among systemic organs. In a recent study, Lamart et al (2021) showed that in rats with americium deposition via wound, administration of Ca-DTPA more effectively inhibited americium retention in the liver compared to the skeleton. However, the data from animal experiments analysed by Lamart et al cover a very short period after wound intake (1-7 days) and should be used with caution for interpretation of long-term trends in tissue retention.…”

Modelling DTPA therapy following Am contamination in rats

“…in the USA (FDA 2015 ), France (Grappin and Bérard 2008 ) and Germany (approved in 2005, marketing authorization number 6813281.00.00 1 ). Numerous animal studies and human studies have provided evidence about the efficacy of DTPA treatment (Volf 1978 ; Catsch 1968 ; Roedler et al 1989 ; Carbaugh et al 1989 ; Grémy et al 2016 , 2021 ; Jech et al 1972 ; Fisher 2000 ; Bhattacharyya et al 1992 ; Bertelli et al 2010 , 2018 ; Breustedt et al 2019 ; Cohen et al 1974 ; Davesne et al 2016 ; Hengé-Napoli et al 2000 ; Grappin et al 2006 ; Gorden et al 2003 ; Durbin et al 2006 ; Stradling et al 2000 ; Fritsch et al 2007 ; James et al 2007 ; Jolly et al 1972 ; Poudel et al 2017 ; Schadilov 2010 ; Schadilov et al 2005 ; Schofield and Lynn 1973 ; Norwood 1960 ; Ohlenschläger et al 1978 ; Lamart et al 2021 ). Side effects and complications associated with DTPA treatments are not uncommon (Taylor et al 2007 ; Glover et al 2022 ).…”