Bisphosphonate Liposomes for Cobalt and Strontium Decorporation?

ABSTRACT: During a nuclear/radiological incident or an accident involving internal intakes with radioactive cobalt or strontium, the recommended treatments, consisting of the administration of diethylenetriaminepentaacetic acid for 60 Co and calcium gluconate for 90 Sr, are of low specificity, and their effectiveness can be enhanced. In this manuscript, a liposomal formulation was developed to deliver potential chelating agents to the main retention organs of both radionuclides. A bisphosphonate, etidronate, has been selected as a possible candidate due to its satisfying decorporation activity for uranium, bone tropism, and potential affinity with cobalt. Pre-clinical studies have been carried out on rats using radionuclide contamination and treatment administration by the intravenous route. The effectiveness of free or liposomal etidronate was evaluated, with an administration at 30 min, 48 h post-contamination with 60 Co. Regarding 85 Sr, a more extended experiment with etidronate liposomes was performed over 6 d. The results were compared to those performed with reference treatments, diethylenetriaminepentaacetic acid for cobalt and calcium gluconate for strontium. Unexpected results were found for the reference treatments that were significantly less effective than previously reported or showed no effectiveness. Free etidronate revealed no significant efficacy after 48 h, but the liposomal form suggested an interaction with radionuclides, not sufficient to change the biokinetics. This study emphasizes the need for early treatment administration and further research to provide a more effective medical countermeasure.

Co-exposure to internal and external radiation alters cesium biokinetics and retention in mice.

Exposures in post-accidental situations are complex and include both external exposure and internal contamination with several radionuclides. However, in vivo and in vitro studies generally use simplified exposures, while a recent study suggested that combined external irradiation and internal contamination may induce more severe biological effects compared to single exposures. In an attempt to test the hypothesis of potential non-additive effects of multiple radiological exposures, we used a mouse model of combined external x-ray irradiation at 1 and 5 Gy and internal contamination with injection of 20 KBq 137Cs. The results showed differential kinetics of 137Cs elimination in irradiated animals compared to sham-irradiated, 137Cs injected animals. Moreover, changes in plasma potassium and in relative testis weight were observed 38 days after irradiation and injection in co-exposed animals compared to 137Cs injection alone. These results demonstrate that an external exposure combined with an internal contamination may lead to unexpected changes in biokinetics of radionuclides and biological effects compared to single exposures.