Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent.
Cetuximab (IMC-C225) is a monoclonal antibody directed against both the wild-type and mutant vIII isoform of the epidermal growth factor receptor (EGFR). The purpose of the present study was to evaluate the monoclonal antibody (MoAb), cetuximab, as a boron delivery agent for neutron capture therapy (NCT) of brain tumors. Twenty-four hours following intratumoral (i.t.) administration of boronated cetuximab (C225-G5-B(1100)), the mean boron concentration in rats bearing either F98(EGFR) or F98(WT) gliomas were 92.3+/-23.3 microg/g and 36.5+/-18.8 microg/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B(1000)) was 6.7+/-3.6 microg/g. Based on its favorable in vivo uptake, C225-G5-B(1100) was evaluated as a delivery agent for BNCT in F98(EGFR) glioma bearing rats. The mean survival time (MST) of rats that received C225-G5-B(1100), administered by convection enhanced delivery (CED), was 45+/-3d compared to 25+/-3d for untreated control animals. A further enhancement in MST to >59d was obtained by administering C225-G5-B(1100) in combination with i.v. boronophenylalanine (BPA). These data are the first to demonstrate the efficacy of a boronated MoAb for BNCT of an intracerebral (i.c.) glioma and are paradigmatic for future studies using a combination of boronated MoAbs and low molecular weight delivery agents.
Barth
Rolf F
RF
Department of Pathology, The Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA. barth.1@osu.edu
Wu
Gong
G
Yang
Weilian
W
Binns
Peter J
PJ
Riley
Kent J
KJ
Patel
Hemant
H
Coderre
Jeffrey A
JA
Tjarks
Werner
W
Bandyopadhyaya
A K
AK
Thirumamagal
B T S
BT
Ciesielski
Michael J
MJ
Fenstermaker
Robert A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001895:Boron; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D000068818:Cetuximab; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D005910:Glioma / Q000378:metabolism* / Q000532:radiotherapy*; D007457:Iodine Radioisotopes; D009154:Mutation; D051381:Rats; D011916:Rats, Inbred F344
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D001895:Boron; D000068818:Cetuximab