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

Appl Radiat Isot. 2004 Nov;61(5):899-903. doi: 10.1016/j.apradiso.2004.05.004.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / radiotherapy*
  • Cetuximab
  • Drug Delivery Systems
  • Epidermal Growth Factor / metabolism*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / immunology
  • Glioma / metabolism*
  • Glioma / radiotherapy*
  • Iodine Radioisotopes
  • Mutation
  • Rats
  • Rats, Inbred F344

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Iodine Radioisotopes
  • Epidermal Growth Factor
  • ErbB Receptors
  • Boron
  • Cetuximab