European Journal of Nuclear Medicine and Molecular Imaging

, Volume 35, Issue 6, pp 1179–1191

Differences in radiosensitivity between three HER2 overexpressing cell lines

Authors

  • Ann-Charlott Steffen
    • Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck LaboratoryUppsala University
  • Lovisa Göstring
    • Affibody AB
  • Vladimir Tolmachev
    • Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck LaboratoryUppsala University
  • Stig Palm
    • Department of Radiation PhysicsSahlgrenska Academy at Göteborg University
  • Bo Stenerlöw
    • Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck LaboratoryUppsala University
    • Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck LaboratoryUppsala University
    • Biomedical Radiation SciencesRudbeck Laboratory
Original Article

DOI: 10.1007/s00259-007-0713-x

Cite this article as:
Steffen, A., Göstring, L., Tolmachev, V. et al. Eur J Nucl Med Mol Imaging (2008) 35: 1179. doi:10.1007/s00259-007-0713-x

Abstract

Purpose

HER2 is a potential target for radionuclide therapy, especially when HER2 overexpressing breast cancer cells are resistant to Herceptin® treatment. Therefore, it is of interest to analyse whether HER2 overexpressing tumour cells have different inherent radiosensitivity.

Methods

The radiosensitivity of three often used HER2 overexpressing cell lines, SKOV-3, SKBR-3 and BT-474, was analysed. The cells were exposed to conventional photon irradiation, low linear energy transfer (LET), to characterise their inherent radiosensitivity. The analysis was made with clonogenic survival and growth extrapolation assays. The cells were also exposed to alpha particles, high LET, from 211At decays using the HER2-binding affibody molecule 211At-(ZHER2:4)2 as targeting agent. Assays for studies of internalisation of the affibody molecule were applied.

Results

SKOV-3 cells were most radioresistant, SKBR-3 cells were intermediate and BT-474 cells were most sensitive as measured with the clonogenic and growth extrapolation assays after photon irradiation. The HER2 dependent cellular uptake of 211At was qualitatively similar for all three cell lines. However, the sensitivity to the alpha particles from 211At differed; SKOV-3 was most resistant, SKBR-3 intermediate and BT-474 most sensitive. These differences were unexpected because it is assumed that all types of cells should have similar sensitivity to high-LET radiation. The sensitivity to alpha particle exposure correlated with internalisation of the affibody molecule and with size of the cell nucleus.

Conclusion

There can be differences in radiosensitivity, which, if they also exist between patient breast cancer cells, are important to consider for both conventional radiotherapy and for HER2-targeted radionuclide therapy.

Keywords

ErbB2 HER2 High LET Nuclear medicine Radiation effects Tumour cells

Copyright information

© Springer-Verlag 2008