TY - JOUR
T1 - In vitro and in vivo evaluation of a novel ferrocyanide functionalized nanopourous silica decorporation agent for cesium in rats
AU - Timchalk, Charles
AU - Creim, Jeffrey A.
AU - Sukwarotwat, Vichaya
AU - Wiacek, Robert
AU - Addleman, R. Shane
AU - Fryxell, Glen E.
AU - Yantasee, Wassana
PY - 2010/9
Y1 - 2010/9
N2 - 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 (SiO2). In vitro experiments focused on the evaluation and optimization of SAMMS for capturing radiocesium (137Cs); 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 137Cs chloride (∼40 μg kg) by intravenous (i.v.) injection or oral gavage; Group II animals were administered pre-bound 137Cs-SAMMS or sequential 137Cs chloride + SAMMS (∼61 ng kg-1) by oral gavage; and Group III was orally administered 137Cs 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 h and blood, urine, and fecal samples were collected for 137Cs analysis (gamma counting). Rats were then humanely euthanized, and selected tissues analyzed. Orally administered 137Cs chloride was rapidly and well absorbed (∼100% relative to i.v. dose), and the pharmacokinetics (blood, urine, feces, and tissues) were very comparable to the i.v. dose group. For both exposures the urine and feces accounted for 20 and 3% of the dose, respectively. The prebound 137Cs-SAMMS was retained primarily within the feces (72% of the dose), with ∼1.4% detected in the urine, suggesting that the 137Cs remained tightly bound to SAMMS. SAMMS and Prussian blue both effectively captured available 137Cs 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 137Cs chloride dose and high sorbent dosage that was utilized. Future studies are planned to optimize the performance of SAMMS in vivo over a broader range of doses and conditions.
AB - 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 (SiO2). In vitro experiments focused on the evaluation and optimization of SAMMS for capturing radiocesium (137Cs); 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 137Cs chloride (∼40 μg kg) by intravenous (i.v.) injection or oral gavage; Group II animals were administered pre-bound 137Cs-SAMMS or sequential 137Cs chloride + SAMMS (∼61 ng kg-1) by oral gavage; and Group III was orally administered 137Cs 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 h and blood, urine, and fecal samples were collected for 137Cs analysis (gamma counting). Rats were then humanely euthanized, and selected tissues analyzed. Orally administered 137Cs chloride was rapidly and well absorbed (∼100% relative to i.v. dose), and the pharmacokinetics (blood, urine, feces, and tissues) were very comparable to the i.v. dose group. For both exposures the urine and feces accounted for 20 and 3% of the dose, respectively. The prebound 137Cs-SAMMS was retained primarily within the feces (72% of the dose), with ∼1.4% detected in the urine, suggesting that the 137Cs remained tightly bound to SAMMS. SAMMS and Prussian blue both effectively captured available 137Cs 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 137Cs chloride dose and high sorbent dosage that was utilized. Future studies are planned to optimize the performance of SAMMS in vivo over a broader range of doses and conditions.
KW - absorption
KW - cesium
KW - chelation
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=77955616904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955616904&partnerID=8YFLogxK
U2 - 10.1097/HP.0b013e3181bca9b0
DO - 10.1097/HP.0b013e3181bca9b0
M3 - Article
C2 - 20699707
AN - SCOPUS:77955616904
SN - 0017-9078
VL - 99
SP - 420
EP - 429
JO - Health Physics
JF - Health Physics
IS - 3
ER -