Application of extracorporeal immunoadsorption to reduce circulating blood radioactivity after intraperitoneal administration of indium-111-HMFG1-biotin.
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.
Wang
Zhongmin
Z
Department of Oncology, Lund University Hospital, Lund, Sweden.
Garkavij
Michael
M
Tennvall
Jan G
JG
Ohlsson
Tomas
T
Strand
Sven-Erik
SE
Sjögren
Hans-Olov
HO
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D019921:Biotinylation; D018796:Immunoconjugates / Q000008:administration & dosage*; D007163:Immunosorbent Techniques; D007205:Indium Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D007263:Infusions, Parenteral; D051379:Mice; D023421:Models, Animal; D011829:Radiation Dosage; D011851:Radioactivity; D051381:Rats
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007205:Indium Radioisotopes; C469215:pemtumomab