In Vitro and in Vivo Evaluation of a Novel Ferrocyanide Functionalized Nanopourous Silica Decorporation Agent for Cesium in Rats

Abstract

Novel decorporation agents are being developed to protect against radiological terrorist attacks. These sorbents, known as the self-assembled monolayer on mesoporous supports (SAMMS ™ ), are hybrid materials where differing organic moieties are grafted onto mesoporous silica (SiO 2 ). In vitro experiments focused on the evaluation, and optimization of SAMMS for capturing radiocesium ( 137 Cs); therefore based on these studies, a ferrocyanide copper (FC-Cu-EDA)-SAMMS was advanced for in vivo evaluation. In vivo experiments were conducted comparing the performance of the SAMMS vs. insoluble Prussian blue. Groups of jugular cannulated rats (4/ treatment) were evaluated. Animals in group I were administered 137 Cs chloride (~40 μg/kg) by intravenous (iv) injection or oral gavage; Group II animals were administered pre-bound 137 Cs-SAMMS or sequential 137 Cs chloride + SAMMS (~61 ng/kg) by oral gavage; and Group III was orally administered 137 Cs chloride (~61 ng/kg) followed by either 0.1 g of SAMMS or Prussian blue. Following dosing, the rats were maintained in metabolism cages for 72 hour and blood, urine and fecal samples were collected for 137 Cs analysis (gamma counting). Rats were then humanely euthanized, and selected tissues analyzed. Orally administered 137 Cs chloride was rapidly and well absorbed (~100% relative to iv dose), and the pharmacokinetics (blood, urine, feces & tissues) were very comparable to the iv dose group. For both exposures the urine and feces accounted for 20 and 3% of the dose, respectively. The prebound 137 Cs-SAMMS was retained primarily within the feces (72% of the dose), with ~1.4% detected in the urine, suggesting that the 137 Cs remained tightly bound to SAMMS. SAMMS & Prussian blue both effectively captured available 137 Cs in the gut with feces accounting for 80-88% of the administered dose, while less than 2% was detected in the urine. This study suggests that the functionalized SAMMS outperforms Prussian blue in vitro at low pH, but demonstrates comparable in vivo sequestration efficacy at low exposure concentrations. The comparable response may be the result of the low 137 Cs chloride dose and high sorbent dosage that was utilized. Future studies are planned to optimize SAMMS in vivo performance over a broader range of doses and conditions.

Complexes of <i>myo</i>-Inositol-Hexakisphosphate (IP6) with Zinc or Lanthanum for the Decorporation of Radiocesium

“…The maximum sorption capacity of Zn-IP6, La-IP6, and PB was estimated to be 203.0, 113.9, and 17.8 mg Cs/g, respectively. In previous reports, the maximum sorption capacity of PB has been reported to be 16.5 mg Cs/g at pH 8.6, 6) 158.5 mg Cs/g, 18) 12.5 mg Cs/g at pH 7.7 in seawater, 19) and 131.6 mg Cs/g, 20) depending on the study. While these values from previous study are different, the results of this study indicate that Zn-IP6 and La-IP6 possess much higher adsorption potency compared to PB, which has been approved as a decorporation agent for radiocesium.…”

“…The biological half-life of 137 Cs is long and is approximately 100 d in male human adults. [6][7][8][9] These properties, coupled with internal exposure of 137 Cs, could be very harmful to humans. When exposure to 137 Cs occurs in humans, decorporation agents are useful for decreasing the absorbed radiation dose.…”

Comparison of Absorbents and Drugs for Internal Decorporation of Radiocesium: Advances of Polyvinyl Alcohol Hydrogel Microsphere Preparations Containing Magnetite and Prussian Blue

“…After binding with the carrier to prevent dissolution of the constituent in the GI tract, 24) these ferrocyanides were examined for decorporation of radiocesium in livestocks in the 1970s. 25,26) Currently, ferrocyanide is applied for the removal of radiocesium from animals 27) or the environment 28,29) by binding with insoluble carriers. Unfortunately, the recent trends of emphasizing the adverse effects 30,31) or allergenic effects 32) of the transition metals have hampered their medical application.…”

Investigation of Magnetic Nanoparticles for the Rapid Extraction and Assay of Alpha-Emitting Radionuclides From Urine: Demonstration of a Novel Radiobioassay Method

“…Low cost and no-to-low toxicity would also benefit sorbent properties, but these are not essential, given that very small quantities (i.e., milligrams per assay) are going to be used in a controlled fashion. This is a demanding list of criteria, but a range of advanced sorbent materials are in development and are being evaluated in the subject labs, with some work published on magnetic nanoparticles (Rutledge et al 2010;Warner et al 2008Warner et al , 2010Yantasee et al 2007) and Self-Assembled Monolayers on Mesoporous Supports (SAMMS) (Addleman et al 2005;Busche et al 2009;Fryxell et al 2007;Johnson et al 2011;Timchalk et al 2010;Yantasee et al 2010). Discussion and description of these novel materials are outside the scope of this work and will be presented elsewhere subsequently.…”