Combined Drug and Surgery Treatment of Plutonium-contaminated Wounds

Abstract

There is an important requirement following accidental actinide contamination of wounds to limit the dissemination and retention of such alpha-emitting radionuclides. To reduce wound and systemic contamination, treatment approaches include chelation therapy with or without wound excision. However, it has been hypothesized that wound excision could lead to increased contaminant release and systemic organ retention. This study in the rat addresses this question. Anesthetized rats were contaminated with plutonium nitrate following wounding by deep incision of hind leg muscle. Excision of tissue at the contaminated site was performed 7 d later with or without Diethylene Triamine Pentaacetic Acid (DTPA) treatment (30 μmol kg⁻¹ i.v.). Pu urinary excretion was then measured for a further 3 d, and animals were euthanized at 14 d after contamination. Tissue samples were evaluated for Pu activity and histology. At 7 d after contamination, around 50% of the initial activity remained at the wound site. An average of 16% of this activity was then removed by surgery. Surgery alone resulted in increased urinary excretion, suggesting release from the wound site, but no subsequent increases in organ retention (bone, liver) were observed at 14 d. Indeed, organ Pu activity was slightly reduced. The combination of surgery and DTPA or DTPA treatment alone was much more effective than excision alone as shown by the markedly increased urinary Pu excretion and decreased tissue levels. This is the first report in an experimental rodent model of resection of Pu-contaminated wound. Urinary excretion data provide evidence for the release of activity as a result of surgery, but this does not appear to lead to further Pu organ retention. However, a combination of prior DTPA treatment with wound excision is particularly effective.

A Simple, Rapid, Comparative Evaluation of Multiple Products for Decontamination of Actinide-contaminated Rat Skin Ex Vivo

“…However, it would be interesting to test these products after washing with TR, for example, in order to try to remove the remaining skin-associated activity. It would also be interesting to include DTPA in the dressing either in gel form or simply by injection into the structure, in addition to testing in an actinide-contaminated wound model with or without surgery (Griffiths et al 2014).…”

Effectiveness of Surgical Excision Following Plutonium-contaminated Wounds: Inferences from Historical Cases

“…The CED averted due to excision calculated in this paper assumes that the increase in dose to the systemic organs, due to release of activity by excision, is negligible. In fact, an animal study (Griffiths et al 2014) found that urinary Pu excretion was increased after partial wound excision, but this was not accompanied by further retention of Pu in bone or liver.…”

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

“…injection (Bistline et al 1972, Piechowski et al 1989. Using this model the efficacy of surgical excision and different DTPA administration protocols (single or repeated, and local or systemic) have been assessed on liver and skeleton retention and urinary excretion of Pu (Griffiths et al 2014a, Griffiths et al 2014b). Data analyses have been mostly descriptive and based on central values (means and standard deviations) over groups of animals with same contamination conditions and treatment regimens.…”