Boronated epidermal growth factor as a delivery agent for neutron capture therapy of EGF receptor positive gliomas.
The purpose of the present study was to further evaluate a boronated dendrimer (BD)-epidermal growth factor bioconjugate (BD-EGF), administered by means of convection enhanced delivery (CED), as a molecular targeting agent for boron neutron capture therapy (BNCT) of the F98(EGFR) glioma. Twenty-four hours following CED of (125)I-labeled BD-EGF 47.4% of the injected dose (ID) was retained in F98(EGFR) gliomas compared to 12.3% in F98(WT) (wildtype) receptor negative tumors. Normal brain values were in the range of 5.9-10.1% ID in the tumor bearing cerebral hemisphere. Boron concentrations in F98(EGFR) gliomas were 22.3 and 11.7 microg/g following CED and i.t. injection, respectively. Based on these results, BNCT studies were initiated at the Massachusetts Institute of Technology nuclear reactor (MITRII). The mean survival time (MST) of rats that received BD-EGF either alone or in combination with boronophenylalanine (BPA), injected i.v., were 53+/-13 d and >61+/-14 d, respectively, compared to 40+/-5 d for BPA alone and 31+/-4 d for irradiated controls. These data show that CED improved the radiobiological effectiveness of BD-EGF and lay the groundwork for future studies using combinations of boron delivery agents for NCT of EGFR(+) gliomas.
Department of Pathology, The Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.
Weilian
W
Yang
Rolf F
RF
Barth
Gong
G
Wu
Achintya K
AK
Bandyopadhyaya
B T S
BT
Thirumamagal
Werner
W
Tjarks
Peter J
PJ
Binns
Kent
K
Riley
Hemant
H
Patel
Jeffrey A
JA
Coderre
Michael J
MJ
Ciesielski
Robert A
RA
Fenstermaker
D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D007275:Injections, Intravenous; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014162:Transfection
C436045:4-dihydroxyborylphenylalanine; D001896:Boron Compounds; D011994:Recombinant Proteins; D010649:Phenylalanine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors