The in vivo fate of a 21 211AT labelled monoclonal antibody witknown specificity in a murine system

Andrew T M Vaughan, Wendy I. Bateman, David R. Fisher

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

A monoclonal antibody reactive against the human transferrin receptor has been labelled with the alpha and X ray emitting isotope Astatine 211. The labelling procedure does not affect the ability of the product to bind to the transferrin receptor on the human leukemic cell line HL60. Using a direct binding assay, 211At labelled antibody can be specifically inhibited from binding to its target cells by excess unlabelled antibody. Furthermore, the binding inhibition demonstrated in this system correlates to enhanced clonogenic survival of these cells, indicating that very few atoms of 211At//cell are required for cell death. Data obtained from labelled antibody injected into mice show that the labelled product in serum retains the ability to bind to HL60 cells in vitro, although tissue distributions of the injected activity implies that some of the radiolabel is lost from the protein. Despite this loss of label, preliminary experiments on the localization of labelled antibody to HL60 cells growing s/c in nude mice show that tumor tissue has a higher specific activity than all other tissues, other than blood, after 12 hours. This suggests that further work on the nature of label degradation in vivo is warranted in the context of potential therapeutic and diagnostic studies.

Original languageEnglish (US)
Pages (from-to)1943-1946
Number of pages4
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume8
Issue number11
DOIs
StatePublished - 1982
Externally publishedYes

Fingerprint

Antibody Specificity
antibodies
Monoclonal Antibodies
Transferrin Receptors
Antibodies
HL-60 Cells
cells
Astatine
astatine isotopes
mice
Alpha Particles
Tissue Distribution
Nude Mice
Isotopes
Cell Survival
products
Cell Death
cultured cells
death
serums

Keywords

  • Astatine monoclonal radioimmunotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

The in vivo fate of a 21 211AT labelled monoclonal antibody witknown specificity in a murine system. / Vaughan, Andrew T M; Bateman, Wendy I.; Fisher, David R.

In: International Journal of Radiation Oncology, Biology, Physics, Vol. 8, No. 11, 1982, p. 1943-1946.

Research output: Contribution to journalArticle

@article{2437d2d443894e1283c7517f1eb4cce8,
title = "The in vivo fate of a 21 211AT labelled monoclonal antibody witknown specificity in a murine system",
abstract = "A monoclonal antibody reactive against the human transferrin receptor has been labelled with the alpha and X ray emitting isotope Astatine 211. The labelling procedure does not affect the ability of the product to bind to the transferrin receptor on the human leukemic cell line HL60. Using a direct binding assay, 211At labelled antibody can be specifically inhibited from binding to its target cells by excess unlabelled antibody. Furthermore, the binding inhibition demonstrated in this system correlates to enhanced clonogenic survival of these cells, indicating that very few atoms of 211At//cell are required for cell death. Data obtained from labelled antibody injected into mice show that the labelled product in serum retains the ability to bind to HL60 cells in vitro, although tissue distributions of the injected activity implies that some of the radiolabel is lost from the protein. Despite this loss of label, preliminary experiments on the localization of labelled antibody to HL60 cells growing s/c in nude mice show that tumor tissue has a higher specific activity than all other tissues, other than blood, after 12 hours. This suggests that further work on the nature of label degradation in vivo is warranted in the context of potential therapeutic and diagnostic studies.",
keywords = "Astatine monoclonal radioimmunotherapy",
author = "Vaughan, {Andrew T M} and Bateman, {Wendy I.} and Fisher, {David R.}",
year = "1982",
doi = "10.1016/0360-3016(82)90453-9",
language = "English (US)",
volume = "8",
pages = "1943--1946",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - The in vivo fate of a 21 211AT labelled monoclonal antibody witknown specificity in a murine system

AU - Vaughan, Andrew T M

AU - Bateman, Wendy I.

AU - Fisher, David R.

PY - 1982

Y1 - 1982

N2 - A monoclonal antibody reactive against the human transferrin receptor has been labelled with the alpha and X ray emitting isotope Astatine 211. The labelling procedure does not affect the ability of the product to bind to the transferrin receptor on the human leukemic cell line HL60. Using a direct binding assay, 211At labelled antibody can be specifically inhibited from binding to its target cells by excess unlabelled antibody. Furthermore, the binding inhibition demonstrated in this system correlates to enhanced clonogenic survival of these cells, indicating that very few atoms of 211At//cell are required for cell death. Data obtained from labelled antibody injected into mice show that the labelled product in serum retains the ability to bind to HL60 cells in vitro, although tissue distributions of the injected activity implies that some of the radiolabel is lost from the protein. Despite this loss of label, preliminary experiments on the localization of labelled antibody to HL60 cells growing s/c in nude mice show that tumor tissue has a higher specific activity than all other tissues, other than blood, after 12 hours. This suggests that further work on the nature of label degradation in vivo is warranted in the context of potential therapeutic and diagnostic studies.

AB - A monoclonal antibody reactive against the human transferrin receptor has been labelled with the alpha and X ray emitting isotope Astatine 211. The labelling procedure does not affect the ability of the product to bind to the transferrin receptor on the human leukemic cell line HL60. Using a direct binding assay, 211At labelled antibody can be specifically inhibited from binding to its target cells by excess unlabelled antibody. Furthermore, the binding inhibition demonstrated in this system correlates to enhanced clonogenic survival of these cells, indicating that very few atoms of 211At//cell are required for cell death. Data obtained from labelled antibody injected into mice show that the labelled product in serum retains the ability to bind to HL60 cells in vitro, although tissue distributions of the injected activity implies that some of the radiolabel is lost from the protein. Despite this loss of label, preliminary experiments on the localization of labelled antibody to HL60 cells growing s/c in nude mice show that tumor tissue has a higher specific activity than all other tissues, other than blood, after 12 hours. This suggests that further work on the nature of label degradation in vivo is warranted in the context of potential therapeutic and diagnostic studies.

KW - Astatine monoclonal radioimmunotherapy

UR - http://www.scopus.com/inward/record.url?scp=0020333332&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020333332&partnerID=8YFLogxK

U2 - 10.1016/0360-3016(82)90453-9

DO - 10.1016/0360-3016(82)90453-9

M3 - Article

VL - 8

SP - 1943

EP - 1946

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 11

ER -