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Title: Investigation of Chitosan for Decorporation of 60Co in the Rat

Abstract

Purpose: The reported investigation is a part of our on-going research aimed at identifying effective in vivo non-toxic decorporation agents and developing new therapies to treat internal contamination with radionuclides. The non-toxic nature of chitosan makes it an especially attractive candidate for unsupervised treatment of the general population in case of radiological/nuclear emergency. In this study, chemically unmodified water-soluble chitosan oligosaccharide of low molecular weight was tested for decorporation of cobalt-60 (Co-60) using a rodent model. Methods: Affinity of chitosan oligosaccharide for Co(II) was tested in vitro under conditions of physiological pH range and ionic strength using combined spectrophotometric and potentiometric titration techniques. Fisher F344 rat model was used for in vivo studies. To evaluate effect of chitosan on ingested Co-60, animals received single oral dose of Co-60 chloride (7 – 13.2 kBq per animal) followed by oral administration of chitosan material (288 – 366 mg per kg body weight); chitosan dosing was repeated in 24 hours. Chitosan was also tested for removal of internalized Co-60. In this study, Co-60 single intravenous injection (7 – 8 kBq per animal) was followed by repetitive oral (300 mg per kg body weight) or intravenous (195 mg per kg body weight) administration ofmore » the chitosan material once daily for 5 days. Control animal groups received a single dose of Co-60 without chelator treatment. Excreta was collected daily. Tissues were collected postmortem and analyzed for radioactivity by gamma counting technique. Results: In vitro experiments confirmed binding of Co(II) by chitosan oligosaccharide, formation of mixed cobalt-chitosan-hydroxide complex species was proposed, and stability constants was calculated. Control in vivo studies indicated that about 71% of ingested Co-60 was excreted in two days predominantly through the gastrointestinal tract. For intravenously administered Co-60, urinal excretion was dominant and was found to decrease linearly with time. The oral administration of chitosan appeared to reduce absorption of ingested Co-60; radioactivity in liver and kidney was reduced by over 50%. Intravenously administered chitosan reduced Co-60 levels (after intravenous dosing) in multiple tissues by 15 – 30 %. Decorporation efficacy of oral chitosan was weak. Conclusion: Commercial chemically-unmodified chitosan oligosaccharide exhibited strong potential for the treatment of oral or systemic cobalt exposure. Further studies are warranted to evaluate the dosing regiment.« less

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
963178
Report Number(s):
PNNL-SA-60934
Journal ID: ISSN 0017-9078; HLTPAO; TRN: US0903108
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Health Physics, 97(2):115-124
Additional Journal Information:
Journal Volume: 97; Journal Issue: 2; Journal ID: ISSN 0017-9078
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; RATS; COBALT 60; DECONTAMINATION; CHITIN; OLIGOSACCHARIDES; MATERIALS TESTING; SORPTIVE PROPERTIES; IN VITRO; IN VIVO; KIDNEYS; LIVER; RADIONUCLIDE KINETICS

Citation Formats

Levitskaia, Tatiana G, Creim, Jeffrey A, Curry, Terry L, Luders, Teresa, Morris, James E, Sinkov, Sergey I, Woodstock, Angela D, and Thrall, Karla D. Investigation of Chitosan for Decorporation of 60Co in the Rat. United States: N. p., 2009. Web. doi:10.1097/01.HP.0000346798.82764.d7.
Levitskaia, Tatiana G, Creim, Jeffrey A, Curry, Terry L, Luders, Teresa, Morris, James E, Sinkov, Sergey I, Woodstock, Angela D, & Thrall, Karla D. Investigation of Chitosan for Decorporation of 60Co in the Rat. United States. doi:10.1097/01.HP.0000346798.82764.d7.
Levitskaia, Tatiana G, Creim, Jeffrey A, Curry, Terry L, Luders, Teresa, Morris, James E, Sinkov, Sergey I, Woodstock, Angela D, and Thrall, Karla D. Sat . "Investigation of Chitosan for Decorporation of 60Co in the Rat". United States. doi:10.1097/01.HP.0000346798.82764.d7.
@article{osti_963178,
title = {Investigation of Chitosan for Decorporation of 60Co in the Rat},
author = {Levitskaia, Tatiana G and Creim, Jeffrey A and Curry, Terry L and Luders, Teresa and Morris, James E and Sinkov, Sergey I and Woodstock, Angela D and Thrall, Karla D},
abstractNote = {Purpose: The reported investigation is a part of our on-going research aimed at identifying effective in vivo non-toxic decorporation agents and developing new therapies to treat internal contamination with radionuclides. The non-toxic nature of chitosan makes it an especially attractive candidate for unsupervised treatment of the general population in case of radiological/nuclear emergency. In this study, chemically unmodified water-soluble chitosan oligosaccharide of low molecular weight was tested for decorporation of cobalt-60 (Co-60) using a rodent model. Methods: Affinity of chitosan oligosaccharide for Co(II) was tested in vitro under conditions of physiological pH range and ionic strength using combined spectrophotometric and potentiometric titration techniques. Fisher F344 rat model was used for in vivo studies. To evaluate effect of chitosan on ingested Co-60, animals received single oral dose of Co-60 chloride (7 – 13.2 kBq per animal) followed by oral administration of chitosan material (288 – 366 mg per kg body weight); chitosan dosing was repeated in 24 hours. Chitosan was also tested for removal of internalized Co-60. In this study, Co-60 single intravenous injection (7 – 8 kBq per animal) was followed by repetitive oral (300 mg per kg body weight) or intravenous (195 mg per kg body weight) administration of the chitosan material once daily for 5 days. Control animal groups received a single dose of Co-60 without chelator treatment. Excreta was collected daily. Tissues were collected postmortem and analyzed for radioactivity by gamma counting technique. Results: In vitro experiments confirmed binding of Co(II) by chitosan oligosaccharide, formation of mixed cobalt-chitosan-hydroxide complex species was proposed, and stability constants was calculated. Control in vivo studies indicated that about 71% of ingested Co-60 was excreted in two days predominantly through the gastrointestinal tract. For intravenously administered Co-60, urinal excretion was dominant and was found to decrease linearly with time. The oral administration of chitosan appeared to reduce absorption of ingested Co-60; radioactivity in liver and kidney was reduced by over 50%. Intravenously administered chitosan reduced Co-60 levels (after intravenous dosing) in multiple tissues by 15 – 30 %. Decorporation efficacy of oral chitosan was weak. Conclusion: Commercial chemically-unmodified chitosan oligosaccharide exhibited strong potential for the treatment of oral or systemic cobalt exposure. Further studies are warranted to evaluate the dosing regiment.},
doi = {10.1097/01.HP.0000346798.82764.d7},
journal = {Health Physics, 97(2):115-124},
issn = {0017-9078},
number = 2,
volume = 97,
place = {United States},
year = {2009},
month = {8}
}