Tumor Biology

, Volume 31, Issue 2, pp 79–87

Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF

  • Heewa Kareem
  • Karl Sandström
  • Ronny Elia
  • Lars Gedda
  • Matti Anniko
  • Hans Lundqvist
  • Marika Nestor
Research Article

DOI: 10.1007/s13277-009-0011-2

Cite this article as:
Kareem, H., Sandström, K., Elia, R. et al. Tumor Biol. (2010) 31: 79. doi:10.1007/s13277-009-0011-2

Abstract

Overexpression of epidermal growth factor receptor (EGFR) in several types of malignant tumors correlates with disease progression. EGFR could, therefore, be an excellent candidate for targeted radionuclide diagnostics. However, the high natural expression of EGFR in the liver may be problematic. The aim of this study was to improve the tumor-to-liver ratio of radiolabeled epidermal growth factor (EGF) by blocking its uptake by the liver with a nonradiolabeled EGFR-targeting molecule in tumor-bearing mice. Intraperitoneally injected nonradiolabeled EGF was first evaluated as a blocking agent, preadministered at various time intervals before intravenous injection of 125I-labeled EGF. The anti-EGFR Affibody molecule (ZEGFR:955)2 was then assessed as a blocking agent of 111In-labeled EGF in a dual isotope study (50, 100, and 200 µg, preadministered 30 or 60 min before 111In-EGF). The 30-min preadministration of nonradiolabeled EGF significantly decreased 125I-EGF uptake in the liver, whereas uptake in the tumor remained unchanged. Furthermore, preadministration of only 50 µg (ZEGFR:955)2 as a blocking agent 30 min before the 111In-EGF decreased the uptake of 111In-EGF by the liver and increased its uptake by the tumor, thereby increasing the tumor-to-liver ratio sixfold. We conclude that the Affibody molecule (ZEGFR:955)2 shows promise as a blocking agent that could enhance the outcome of radionuclide-based EGFR-expressing tumor diagnostics and imaging.

Keywords

Affibody moleculeEGFEGFRHNSCCImagingTumor-to-liver ratio

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Heewa Kareem
    • 1
    • 2
  • Karl Sandström
    • 1
  • Ronny Elia
    • 2
  • Lars Gedda
    • 2
  • Matti Anniko
    • 1
  • Hans Lundqvist
    • 2
  • Marika Nestor
    • 1
    • 2
  1. 1.Unit of Otolaryngology and Head & Neck Surgery, Department of Surgical SciencesUppsala University, Akademiska SjukhusetUppsalaSweden
  2. 2.Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology, and Clinical ImmunologyUppsala UniversityUppsalaSweden