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Cellular uptake of radioiodine delivered by trastuzumab can be modified by the addition of epidermal growth factor.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
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2005 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 32, no 7, 771-7 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The purpose of this study was to analyse whether non-radiolabelled epidermal growth factor (EGF) can modify the cellular uptake of 125I when delivered as [125I]trastuzumab. 125I was used as a marker for the diagnostically and therapeutically more interesting isotopes 123I (SPECT), 124I (PET) and 131I (therapy). METHODS: The cell-associated radioactivity was measured in squamous carcinoma A431 cells following addition of [125I]trastuzumab. Different concentrations of [125I]trastuzumab and unlabelled EGF were used, and the total, membrane-bound and internalised radioactivity was measured. We also analysed how EGF and trastuzumab affected the cell growth. RESULTS: It was generally found that the cellular 125I uptake was decreased by the addition of EGF when [125I]trastuzumab was added for short incubation times. However, if the incubation times were longer, EGF increased the 125I uptake. This shift came earlier when higher [125I]trastuzumab concentrations were applied. The addition of EGF also influenced cell proliferation, and concentrations above 10 ng/ml reduced cell growth by approximately 20% after 24 h of incubation. CONCLUSION: By adding unlabelled EGF, it was possible to modify the cellular uptake of [125I]trastuzumab. This points towards new approaches for the modification of radionuclide uptake in EGFR- and HER2-positive tumours.

Place, publisher, year, edition, pages
2005. Vol. 32, no 7, 771-7 p.
Keyword [en]
Antibodies; Monoclonal/*administration & dosage/chemistry, Antineoplastic Agents/*administration & dosage, Cell Line; Tumor, Cell Membrane/metabolism, Cell Proliferation, Dose-Response Relationship; Drug, Epidermal Growth Factor/*administration & dosage/metabolism, Humans, Iodine Radioisotopes/*pharmacokinetics, Ligands, Positron-Emission Tomography, Receptor; Epidermal Growth Factor/metabolism, Receptor; erbB-2/metabolism, Time Factors, Tomography; Emission-Computed; Single-Photon, Tumor Markers; Biological
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-80492DOI: 10.1007/s00259-005-1761-8PubMedID: 15765233OAI: oai:DiVA.org:uu-80492DiVA: diva2:108406
Available from: 2007-02-12 Created: 2007-02-12 Last updated: 2010-09-10Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=15765233&dopt=Citation

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Nordberg, ErikaSteffen, Ann-CharlottPersson, MikaelSundberg, Åsa L.Carlsson, JörgenGlimelius, Bengt

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Nordberg, ErikaSteffen, Ann-CharlottPersson, MikaelSundberg, Åsa L.Carlsson, JörgenGlimelius, Bengt
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