Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent

• Published in: Applied radiation and isotopes 2004-11, Vol.61 (5), p.899-903
• Main Authors: Barth, Rolf F, Wu, Gong, Yang, Weilian, Binns, Peter J, Riley, Kent J, Patel, Hemant, Coderre, Jeffrey A, Tjarks, Werner, Bandyopadhyaya, A.K, Thirumamagal, B.T.S, Ciesielski, Michael J, Fenstermaker, Robert A
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Boron; Boron Neutron Capture Therapy - methods; Boronated cetuximab (anti-EGFR MoAb); Brain Neoplasms - metabolism; Brain Neoplasms - radiotherapy; Cetuximab; Drug Delivery Systems; Epidermal Growth Factor - metabolism; F98 EGFR glioma; Glioma - metabolism; Glioma - radiotherapy; Iodine Radioisotopes; Mutation; Neutron capture therapy; Rats; Rats, Inbred F344; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - immunology
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2004.05.004

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 μg/g and 36.5±18.8 μg/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B 1000) was 6.7±3.6 μg/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±3 d compared to 25±3 d for untreated control animals. A further enhancement in MST to >59 d 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.