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Journal of Neuro-Oncology

, Volume 77, Issue 1, pp 33–45 | Cite as

Planning for Intracavitary Anti-EGFR Radionuclide Therapy of Gliomas. Literature Review and Data on EGFR Expression

  • Carlsson J
  • Ren Z.P
  • Wester K
  • Sundberg Å.L
  • Heldin N.E
  • Hesselager G
  • Persson M
  • Gedda L
  • Tolmachev V
  • Lundqvist H
  • Blomquist E
  • Nistér M
Clinical Study

Summary

Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.

Keywords

EGFR glioma intracavitary locoregional radionuclide therapy 

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Copyright information

© Springer 2005

Authors and Affiliations

  • Carlsson J
    • 1
  • Ren Z.P
    • 2
  • Wester K
    • 1
  • Sundberg Å.L
    • 1
  • Heldin N.E
    • 2
  • Hesselager G
    • 3
  • Persson M
    • 1
  • Gedda L
    • 1
  • Tolmachev V
    • 1
  • Lundqvist H
    • 1
  • Blomquist E
    • 1
  • Nistér M
    • 2
    • 4
  1. 1.Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical ImmunologyRudbeck Laboratory, Uppsala UniversityUppsalaSweden
  2. 2.Unit of Molecular Pathology, Department of Genetics and PathologyRudbeck Laboratory, Uppsala UniversityUppsalaSweden
  3. 3.Unit of Neurosurgery, Department of NeuroscienceUppsala University HospitalUppsalaSweden
  4. 4.Department of Oncology PathologyCancer Centre Karolinska, Karolinska Institutet, Karolinska University Hospital - SolnaStockholmSweden

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