Jun 1, 2002 - We thank Michelle Smith for secretarial assistance in the preparation of this manuscript and Drs. Melvin L. Moeschberger and Amy K. Ferketich ...
[CANCER RESEARCH 62, 3159 –3166, June 1, 2002]
Molecular Targeting of the Epidermal Growth Factor Receptor for Neutron Capture Therapy of Gliomas1 Rolf. F. Barth,2 Weilian Yang, Dianne M. Adams, Joan H. Rotaru, Supriya Shukla, Masaru Sekido, Werner Tjarks, Robert A. Fenstermaker, Michael Ciesielski, Marta M. Nawrocky, and Jeffrey A. Coderre3 Department of Pathology [R. F. B., W. Y., D. M. A., J. H. R.] and the College of Pharmacy [S. S., M. S., W. T.], The Ohio State University, Columbus, Ohio 43210; Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York 14263 [R. A. F., M. C.]; and Medical Department, Brookhaven National Laboratory, Upton, New York 11973 [M. M. N., J. A. C.]
ABSTRACT
INTRODUCTION
Success of boron neutron capture therapy (BNCT) is dependent on cellular and molecular targeting of sufficient amounts of boron-10 to sustain a lethal 10B (n, ␣) 7Li capture reaction. The purpose of the present study was to determine the efficacy of boronated epidermal growth factor (EGF) either alone or in combination with boronophenylalanine (BPA) as delivery agents for an epidermal growth factor receptor (EGFR) -positive glioma, designated F98EGFR. A heavily boronated precision macromolecule [boronated starburst dendrimer (BSD)] was chemically linked to EGF by heterobifunctional reagents. Either F98 wild-type (F98WT) receptor (ⴚ) or EGFR gene-transfected F98EGFR cells, which expressed 5 ⴛ 105 receptor sites/cell, were stereotactically implanted into the brains of Fischer rats, and 2 weeks later biodistribution studies were initiated. For biodistribution studies rats received an intratumoral (i.t.) injection of 125I-labeled BSD-EGF and were euthanized either 6 or 24 h later. At 6 h, equivalent amounts of BSD-EGF were detected in F98EGFR and F98WT tumors. Persistence of the bioconjugate in F98EGFR tumors was specifically determined by EGFR expression. By 24 h 33.2% of injected dose/g of EGF-BSD was retained by F98EGFR gliomas compared with 9.4% % of injected dose/g in F98WT gliomas, and the corresponding boron concentrations were 21.1 g/g and 9.2 g/g, respectively. Boron concentrations in normal brain, blood, liver, kidneys, and spleen all were at nondetectable levels (
