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Title: Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

Abstract

The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of {sup 10}B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10{sup 5} {minus}10{sup 6} EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10{sup 8} boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight ({approximately} 6 kD), this has allowed us to construct relatively small bioconjugates containing {approximately} 900 boron atoms per EGF molecule{sup 3}, which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using {sup 131}I{minus} or {sup 99m}{Tc}-labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of themore » conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma.« less

Authors:
; ; ; ;  [1];  [2]
  1. Ohio State Univ., Columbus, OH (United States)
  2. Uppsala Univ. (Sweden). Dept. of Radiation Sciences
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE, Washington, DC (United States)
OSTI Identifier:
207597
Report Number(s):
BNL-62807; CONF-9410281-4
ON: DE96008212; TRN: 96:009495
DOE Contract Number:  
AC02-76CH00016
Resource Type:
Conference
Resource Relation:
Conference: 6. international symposium on neutron capture therapy for cancer, Kobe (Japan), 31 Oct - 4 Nov 1994; Other Information: PBD: [1994]
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; 40 CHEMISTRY; GLIOMAS; RADIOISOTOPE SCANNING; GROWTH FACTORS; LABELLING; BRAIN; BORON COMPOUNDS; IODINE 125; RATS; TISSUE DISTRIBUTION; TECHNETIUM 99; EXPERIMENTAL NEOPLASMS

Citation Formats

Capala, J, Barth, R F, Adams, D M, Bailey, M Q, Soloway, A H, and Carlsson, J. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas. United States: N. p., 1994. Web.
Capala, J, Barth, R F, Adams, D M, Bailey, M Q, Soloway, A H, & Carlsson, J. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas. United States.
Capala, J, Barth, R F, Adams, D M, Bailey, M Q, Soloway, A H, and Carlsson, J. 1994. "Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas". United States. https://www.osti.gov/servlets/purl/207597.
@article{osti_207597,
title = {Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas},
author = {Capala, J and Barth, R F and Adams, D M and Bailey, M Q and Soloway, A H and Carlsson, J},
abstractNote = {The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of {sup 10}B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10{sup 5} {minus}10{sup 6} EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10{sup 8} boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight ({approximately} 6 kD), this has allowed us to construct relatively small bioconjugates containing {approximately} 900 boron atoms per EGF molecule{sup 3}, which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using {sup 131}I{minus} or {sup 99m}{Tc}-labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma.},
doi = {},
url = {https://www.osti.gov/biblio/207597}, journal = {},
number = ,
volume = ,
place = {United States},
year = {Sat Dec 31 00:00:00 EST 1994},
month = {Sat Dec 31 00:00:00 EST 1994}
}

Conference:
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