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Improving radioimmunotargeting of tumors : the impact of extracorporeal immunoadsorption and preload in rats

Garkavij, Michael LU (1996)
Abstract
In radioimmunotherapy of tumors, uptake of the monoclonal antibody (MAb) used is often too low in relation to its uptake in normal tissues. The purpose of these studies was to improve experimental tumor radioimmunotargeting with (a) extracorporeal immunoadsorption (ECIA), where excess of radiolabeled MAbs circulating in blood is removed, (b) or by preload with unlabeled MAb prior to injection of radiolabeled MAb, (c) or by a combination of these. ECIA based on the avidin-biotin concept enables direct adsorption of radiolabeled and biotinylated MAb from blood and increases the tumor-to-normal tissue (T/N) uptake ratio by reducing background radioactivity in radiosensitive organs. 267 rats (athymic or Brown Norwegian) grafted with human... (More)
In radioimmunotherapy of tumors, uptake of the monoclonal antibody (MAb) used is often too low in relation to its uptake in normal tissues. The purpose of these studies was to improve experimental tumor radioimmunotargeting with (a) extracorporeal immunoadsorption (ECIA), where excess of radiolabeled MAbs circulating in blood is removed, (b) or by preload with unlabeled MAb prior to injection of radiolabeled MAb, (c) or by a combination of these. ECIA based on the avidin-biotin concept enables direct adsorption of radiolabeled and biotinylated MAb from blood and increases the tumor-to-normal tissue (T/N) uptake ratio by reducing background radioactivity in radiosensitive organs. 267 rats (athymic or Brown Norwegian) grafted with human adenocarcinoma or rat colon adenocarcinoma tumors intramuscularly, and beneath the kidney or liver capsule were included in the studies. Of these rats, 82 were subjected to ECIA. Two radioiodinated and biotinylated MAbs, murine L6 or chimeric BR96, were used and evaluated. (I) Using 50 µg dosage of L6, ECIA reduced whole body and plasma activity as well as improved the detectability of subrenal capsule tumors. T/N uptake ratios were increased on average 3 times. (II) The efficacy of ECIA in removing different injected amounts of L6 from plasma was similar. The highest T/N ratios persisting 24h after start of the ECIA were obtained by using 10 µg of 125I-L6-biotin. (III) The efficacy of preload in enhancing tumor uptake and simultaneously decreasing uptake in normal tissues was obtained with 250µg of 125I-L6 preceded by a preload of 50µg unlabeled L6 only. (IV) The effects on radioimmunotargeting of preload and ECIA in combination were synergistic and improved T/N uptake ratios up to 17 times. (V) As compared with ECIA, a new method of whole blood immunoadsorption (WBIA) was technically easier to perform, safer and more reliable, but of approx. comparable efficiency. (VI) WBIA was even applicable on the internalizing and highly tumor selective 125I-BR96-biotin MAb, resulting in manifestly improved T/N ratios. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Professor Stigbrand, Torgny
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Cytology, preload., immunoadsorption, MAb, rat, Tumor, radioimmunotargeting, oncology, cancerology, Cytologi, onkologi, cancer
pages
114 pages
defense location
Lecture hall at the Dept. of Oncology
defense date
1996-05-14 09:30
external identifiers
  • Other:ISRN: LUMEDW/MEOK-1019-SE
ISBN
91-628-1975-5
language
English
LU publication?
yes
id
d18c47e3-fa81-49e4-a97a-3956b64bd49b (old id 28357)
date added to LUP
2007-06-11 13:14:03
date last changed
2016-09-19 08:45:16
@misc{d18c47e3-fa81-49e4-a97a-3956b64bd49b,
  abstract     = {In radioimmunotherapy of tumors, uptake of the monoclonal antibody (MAb) used is often too low in relation to its uptake in normal tissues. The purpose of these studies was to improve experimental tumor radioimmunotargeting with (a) extracorporeal immunoadsorption (ECIA), where excess of radiolabeled MAbs circulating in blood is removed, (b) or by preload with unlabeled MAb prior to injection of radiolabeled MAb, (c) or by a combination of these. ECIA based on the avidin-biotin concept enables direct adsorption of radiolabeled and biotinylated MAb from blood and increases the tumor-to-normal tissue (T/N) uptake ratio by reducing background radioactivity in radiosensitive organs. 267 rats (athymic or Brown Norwegian) grafted with human adenocarcinoma or rat colon adenocarcinoma tumors intramuscularly, and beneath the kidney or liver capsule were included in the studies. Of these rats, 82 were subjected to ECIA. Two radioiodinated and biotinylated MAbs, murine L6 or chimeric BR96, were used and evaluated. (I) Using 50 µg dosage of L6, ECIA reduced whole body and plasma activity as well as improved the detectability of subrenal capsule tumors. T/N uptake ratios were increased on average 3 times. (II) The efficacy of ECIA in removing different injected amounts of L6 from plasma was similar. The highest T/N ratios persisting 24h after start of the ECIA were obtained by using 10 µg of 125I-L6-biotin. (III) The efficacy of preload in enhancing tumor uptake and simultaneously decreasing uptake in normal tissues was obtained with 250µg of 125I-L6 preceded by a preload of 50µg unlabeled L6 only. (IV) The effects on radioimmunotargeting of preload and ECIA in combination were synergistic and improved T/N uptake ratios up to 17 times. (V) As compared with ECIA, a new method of whole blood immunoadsorption (WBIA) was technically easier to perform, safer and more reliable, but of approx. comparable efficiency. (VI) WBIA was even applicable on the internalizing and highly tumor selective 125I-BR96-biotin MAb, resulting in manifestly improved T/N ratios.},
  author       = {Garkavij, Michael},
  isbn         = {91-628-1975-5},
  keyword      = {Cytology,preload.,immunoadsorption,MAb,rat,Tumor,radioimmunotargeting,oncology,cancerology,Cytologi,onkologi,cancer},
  language     = {eng},
  pages        = {114},
  title        = {Improving radioimmunotargeting of tumors : the impact of extracorporeal immunoadsorption and preload in rats},
  year         = {1996},
}