Molecular Targeting and Treatment of an Epidermal Growth Factor Receptor–Positive Glioma Using Boronated Cetuximab

• Published in: Clinical cancer research 2007-02, Vol.13 (4), p.1260-1268
• Main Authors: GONG WU, WEILIAN YANG, MING YANG, CHRISTOFORIDIS, Gregory A, SFERRA, Thomas J, BINNS, Peter J, RILEY, Kent J, CIESIELSKI, Michael J, FENSTERMAKER, Robert A, BARTH, Rolf F, KAWABATA, Shinji, SWINDALL, Michele, BANDYOPADHYAYA, Achintya K, TJARKS, Werner, KHORSANDI, Behrooz, BLUE, Thomas E, FERKETICH, Amy K
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antineoplastic agents; Biological and medical sciences; Boron Compounds - administration & dosage; Boron Compounds - chemistry; Boron Compounds - pharmacokinetics; Boron Neutron Capture Therapy - methods; boronated cetuximab; Cetuximab; Combined Modality Therapy; Dendrimers - administration & dosage; Dendrimers - chemistry; Dendrimers - pharmacokinetics; EGFR; F98; Glioma - drug therapy; Glioma - metabolism; Glioma - radiotherapy; Humans; Immunoconjugates - pharmacokinetics; Immunoconjugates - pharmacology; Magnetic Resonance Imaging - methods; Medical sciences; Neurology; neutron capture therapy; Pharmacology. Drug treatments; rat glioma; Rats; Rats, Inbred F344; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - immunology; Receptor, Epidermal Growth Factor - metabolism; Tissue Distribution; Tumors of the nervous system. Phacomatoses
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-2399

Purpose: The purpose of the present study was to evaluate the anti–epidermal growth factor monoclonal antibody (mAb) cetuximab (IMC-C225) as a delivery agent for boron neutron capture therapy (BNCT) of a human epidermal growth factor receptor (EGFR) gene-transfected rat glioma, designated as F98 EGFR . Experimental Design: A heavily boronated polyamidoamine dendrimer was chemically linked to cetuximab by means of the heterobifunctional reagents N -succinimidyl 3-(2-pyridyldithio)-propionate and N -(k-maleimido undecanoic acid)-hydrazide. The bioconjugate, designated as BD-C225, was specifically taken up by F98 EGFR glioma cells in vitro compared with receptor-negative F98 wild-type cells (41.8 versus 9.1 μg/g). For in vivo biodistribution studies, F98 EGFR cells were implanted stereotactically into the brains of Fischer rats, and 14 days later, BD-C225 was given intracerebrally by either convection enhanced delivery (CED) or direct intratumoral (i.t.) injection. Results: The amount of boron retained by F98 EGFR gliomas 24 h following CED or i.t. injection was 77.2 and 50.8 μg/g, respectively, with normal brain and blood boron values