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Application of extracorporeal immunoadsorption to reduce circulating blood radioactivity after intraperitoneal administration of indium-111-HMFG1-biotin.

Wang, Zhongmin LU ; Garkavij, Michael LU ; Tennvall, Jan LU ; Ohlsson, Tomas G LU ; Strand, Sven-Erik LU and Sjögren, Hans Olov LU (2002) In Cancer 94(4 Suppl). p.1287-1292
Abstract
BACKGROUND: Extracorporeal immunoadsorption (ECAT) is a method of reducing activity in radiosensitive organs by removing excess monoclonal antibodies (MAbs) from the blood. Previously, the authors experimentally evaluated ECAT based on the avidin-biotin concept after intravenous administration of radioimmunoconjugates. The aim of the current study was to determine whether ECAT could be used to reduce activity after intraperitoneal (i.p.) administration of indium-111((111)In)-HMFG1-biotin in rats, and to compare the pharmacokinetics of (111)In-HMFG1 with or without attached biotin after i.p. injection. METHODS: HMFG1, a murine immunoglobulin G(1) MAb that recognizes an epitope on the polymorphic epithelial mucin (PEM) antigen, was labeled... (More)
BACKGROUND: Extracorporeal immunoadsorption (ECAT) is a method of reducing activity in radiosensitive organs by removing excess monoclonal antibodies (MAbs) from the blood. Previously, the authors experimentally evaluated ECAT based on the avidin-biotin concept after intravenous administration of radioimmunoconjugates. The aim of the current study was to determine whether ECAT could be used to reduce activity after intraperitoneal (i.p.) administration of indium-111((111)In)-HMFG1-biotin in rats, and to compare the pharmacokinetics of (111)In-HMFG1 with or without attached biotin after i.p. injection. METHODS: HMFG1, a murine immunoglobulin G(1) MAb that recognizes an epitope on the polymorphic epithelial mucin (PEM) antigen, was labeled with (111)In and then biotinylated. ECAT was explored from unseparated blood using an avidin-agarose adsorption column. Thirty rats were used as controls and 13 underwent ECAT. The whole-body (WB), blood, and organ activity were monitored. RESULTS: The binding capacity of (111)In-HMFG1-biotin to avidin was high. Biotinylation did not enhance the excretion of HMFG1. When ECAT was employed, the WB and blood radioactivity were reduced by 35-40% (P < 0.05) and 75--86% (P < 0.01), respectively. After the completion of ECAT, the activity uptake in organs was significantly decreased. CONCLUSIONS: ECAT was successfully applied after i.p. injection of the (111)In-HMFG-biotin MAb to reduce the radioactivity in the WB, blood, and radiosensitive organs. Due to redistribution of the radiolabeled MAbs during and after the completion of ECAT, the adsorption may have been prolonged or repeated. Biotinylation did not significantly change the biodistribution of the (111)In-HMFG1 in rats after intraperitoneal injection. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
Non-U.S. Gov't, Support, Rats, Radioactivity, Animal, Radiation Dosage, Models, Mice, Parenteral, Infusions, Indium Radioisotopes/*administration & dosage/chemistry, Biotinylation, *Immunosorbent Techniques, Immunoconjugates/*administration & dosage, Antibodies, Monoclonal/chemistry/immunology
in
Cancer
volume
94
issue
4 Suppl
pages
1287 - 1292
publisher
John Wiley & Sons
external identifiers
  • pmid:11877758
  • wos:000173958100015
  • scopus:0037083368
ISSN
1097-0142
DOI
10.1002/cncr.10298
language
English
LU publication?
yes
id
2bdb291b-855c-47d8-9d74-08fd91e3c03f (old id 106356)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11877758&dopt=Abstract
date added to LUP
2007-07-19 11:00:43
date last changed
2017-07-02 03:38:52
@article{2bdb291b-855c-47d8-9d74-08fd91e3c03f,
  abstract     = {BACKGROUND: Extracorporeal immunoadsorption (ECAT) is a method of reducing activity in radiosensitive organs by removing excess monoclonal antibodies (MAbs) from the blood. Previously, the authors experimentally evaluated ECAT based on the avidin-biotin concept after intravenous administration of radioimmunoconjugates. The aim of the current study was to determine whether ECAT could be used to reduce activity after intraperitoneal (i.p.) administration of indium-111((111)In)-HMFG1-biotin in rats, and to compare the pharmacokinetics of (111)In-HMFG1 with or without attached biotin after i.p. injection. METHODS: HMFG1, a murine immunoglobulin G(1) MAb that recognizes an epitope on the polymorphic epithelial mucin (PEM) antigen, was labeled with (111)In and then biotinylated. ECAT was explored from unseparated blood using an avidin-agarose adsorption column. Thirty rats were used as controls and 13 underwent ECAT. The whole-body (WB), blood, and organ activity were monitored. RESULTS: The binding capacity of (111)In-HMFG1-biotin to avidin was high. Biotinylation did not enhance the excretion of HMFG1. When ECAT was employed, the WB and blood radioactivity were reduced by 35-40% (P &lt; 0.05) and 75--86% (P &lt; 0.01), respectively. After the completion of ECAT, the activity uptake in organs was significantly decreased. CONCLUSIONS: ECAT was successfully applied after i.p. injection of the (111)In-HMFG-biotin MAb to reduce the radioactivity in the WB, blood, and radiosensitive organs. Due to redistribution of the radiolabeled MAbs during and after the completion of ECAT, the adsorption may have been prolonged or repeated. Biotinylation did not significantly change the biodistribution of the (111)In-HMFG1 in rats after intraperitoneal injection.},
  author       = {Wang, Zhongmin and Garkavij, Michael and Tennvall, Jan and Ohlsson, Tomas G and Strand, Sven-Erik and Sjögren, Hans Olov},
  issn         = {1097-0142},
  keyword      = {Non-U.S. Gov't,Support,Rats,Radioactivity,Animal,Radiation Dosage,Models,Mice,Parenteral,Infusions,Indium Radioisotopes/*administration & dosage/chemistry,Biotinylation,*Immunosorbent Techniques,Immunoconjugates/*administration & dosage,Antibodies,Monoclonal/chemistry/immunology},
  language     = {eng},
  number       = {4 Suppl},
  pages        = {1287--1292},
  publisher    = {John Wiley & Sons},
  series       = {Cancer},
  title        = {Application of extracorporeal immunoadsorption to reduce circulating blood radioactivity after intraperitoneal administration of indium-111-HMFG1-biotin.},
  url          = {http://dx.doi.org/10.1002/cncr.10298},
  volume       = {94},
  year         = {2002},
}