Combined drug and surgery treatment of plutonium-contaminated wounds: indications obtained using a rodent model.

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.

Increased retention of americium in kidneys as compared with plutonium in an actinide wound contamination model in the rat.

PURPOSE: Americium-241 ((241)Am) presents a potential risk for nuclear industry workers associated with reactor decommissioning and aging combustible materials. The purpose of this study was to investigate Am renal retention after actinide contamination by wounding in the rat. MATERIALS AND METHODS: Anesthetized rats were contaminated with Mixed Oxide (MOX) (7.1% Plutonium [Pu] by mass and containing 27% Am as % total alpha activity), Pu or Am nitrate following an incision wound of the hind leg. Times of euthanasia ranged from 2 hours to 5 months after contamination. Pu and Am levels were quantified following radiochemistry and alpha-spectrophotometry. RESULTS: Initial data show that over the experimental period the proportion of Am in kidneys as a fraction of total kidney alpha activity was elevated as compared to MOX powder indicating a specific retention in this organ. The percentage of Pu was similar to the powder. After MOX contamination, kidney to liver ratios appeared to increase more markedly for Am (from 0.2 at 7 days to 0.6 at 90 days) as compared with Pu (0.1 at 7 days to 0.2 at 90 days). In accordance with tissue actinide retention the dose from Am to the kidney increases with time. For comparison, the ratio of estimated equivalent doses due to Am to kidney is 1.5-fold greater than for Pu (around 90 versus 60 mSv). CONCLUSION: After actinide contamination of wounds, Am is concentrated in the kidneys as compared to Pu leading to potential exposure of renal tissue to both alpha particles and gamma radiation.

Actinide handling after wound entry with local or systemic decorporation therapy in the rat.

BACKGROUND: Treatment of actinide-contaminated wounds may be problematic because of contaminant physicochemical properties, dissemination and anatomical localization. This study investigates different chelation/resection protocols after contamination of rats with americium (Am) or plutonium (Pu) nitrate or mixed oxide (MOX; uranium (U), Pu oxide). METHODS: Anesthetized rats were contaminated with Am or Pu nitrate (moderately soluble) or MOX (insoluble) following wounding of hind leg muscle. DTPA (diethylene triamine pentaacetic acid) treatment (30 µmol/kg) was immediate or delayed, systemic or local and combined or not with wound resection. Actinide urinary and tissue levels were measured. RESULTS: Comparison of Pu nitrate and MOX dissemination at the wound site indicated a more heterogeneous localization of MOX particles. In all cases DTPA treatment reduced target tissue (bone, liver) activity levels even if DTPA treatment was started 7 days after contamination. Surgery alone increased urinary excretion suggesting release from the wound site but no subsequent increases in organ retention (bone, liver) were observed. The combination of surgery and DTPA increased Pu excretion and reduced tissue levels markedly. CONCLUSION: This rodent model of actinide wound contamination has been used to test different treatments. It provides evidence of activity release as a result of surgery that seems not to lead to increased organ retention.