Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF
2010 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 31, no 2, 79-87 p.Article in journal (Refereed) Published
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 tumorbearing 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 200μg, 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 50μg (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 EGFRexpressing tumor diagnostics and imaging.
Place, publisher, year, edition, pages
Springer , 2010. Vol. 31, no 2, 79-87 p.
Affibody molecule, EGF, EGFR, HNSCC, Imaging, Tumor-to-liver ratio
Cancer and Oncology
Research subject Biomedical Radiation Science
IdentifiersURN: urn:nbn:se:uu:diva-156520DOI: 10.1007/s13277-009-0011-2ISI: 000278160700002PubMedID: 20358420OAI: oai:DiVA.org:uu-156520DiVA: diva2:432050