Neutron capture therapy of epidermal growth factor (plus) 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 mug/g and 36.5 +/- 18.8 mug/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B-1000) was 6.7 +/- 3.6 mug/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 > 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. (C) 2004 Elsevier Ltd. All rights reserved.