Radioactive EGFR Antibody Cetuximab in Multimodal Cancer Treatment: Stability and Synergistic Effects With Radiotherapy

Dirk Rades, Christian Wolff, Roger Nadrowitz, Christian Breunig, Steven E. Schild, Manfred Baehre, Birgit Meller

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Purpose: Systemic therapies when added to whole brain radiotherapy have failed to improve the survival of patients with multiple brain metastases. The epidermal growth factor receptor antibody cetuximab is an attractive option, if it is able to cross the blood-brain barrier. This might be proven with molecular imaging if the radiolabeled antibody is stable long enough to be effective. This study investigated the stability of radiolabeled cetuximab (Erbitux) (131I-Erbi) and potential synergistic effects with radiotherapy in vitro. Methods and Materials: Two cell lines were investigated, A431 with numerous epidermal growth factor receptors, and JIMT without epidermal growth factor receptors. We labeled 0.4 mg cetuximab with 50 MBq of [131I] iodide. Stability was determined for 72 h. The cell cultures were incubated with 131I-Erbi or cold cetuximab for 72 h. Uptake and cell proliferation were measured every 24 h after no radiotherapy or irradiation with 2, 4, or 10 Gy. Results: The radiolabeling yield of 131I-Erbi was always >80%. The radiochemical purity was still 93.6% after 72 h. A431 cells showed a 131I-Erbi uptake about 100-fold greater than the JIMT controls. After 48 h, the A431 cultures showed significantly decreased proliferation. At 72 h after irradiation, 131I-Erbi resulted in more pronounced inhibition of cell proliferation than the cold antibody in all radiation dose groups. Conclusion: 131I-Erbi was stable for ≤72 h. Radiotherapy led to increased tumor cell uptake of 131I-Erbi. Radiotherapy and 131I-Erbi synergistically inhibited tumor cell proliferation. These results provide the prerequisite data for a planned in vivo study of whole brain radiotherapy plus cetuximab for brain metastases.

Original languageEnglish (US)
Pages (from-to)1226-1231
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume75
Issue number4
DOIs
StatePublished - Nov 15 2009

Keywords

  • Blood-brain barrier
  • Cetuximab
  • EGFR
  • Molecular imaging
  • Radioactive epidermal growth factor receptor antibody
  • Stability

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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