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PET imaging of epidermal growth factor receptor expression in tumours using 89Zr-labelled ZEGFR: 2377 affibody molecules.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. (Vladimir Tolmachev)
KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging. (Anna Orlova)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. (Vladimir Tolmachev)
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2016 (English)In: International journal of oncology, ISSN 1791-2423, Vol. 48, no 4, 1325-1332 p.Article in journal (Refereed) Published
Abstract [en]

Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor, which is overexpressed in many types of cancer. The use of EGFR-targeting monoclonal antibodies and tyrosine-kinase inhibitors improves significantly survival of patients with colorectal, non-small cell lung cancer and head and neck squamous cell carcinoma. Detection of EGFR overexpression provides important prognostic and predictive information influencing management of the patients. The use of radionuclide molecular imaging would enable non-invasive repeatable determination of EGFR expression in disseminated cancer. Moreover, positron emission tomography (PET) would provide superior sensitivity and quantitation accuracy in EGFR expression imaging. Affibody molecules are a new type of imaging probes, providing high contrast in molecular imaging. In the present study, an EGFR-binding affibody molecule (ZEGFR:2377) was site-specifically conjugated with a deferoxamine (DFO) chelator and labelled under mild conditions (room temperature and neutral pH) with a positron-emitting radionuclide 89Zr. The 89Zr-DFO-ZEGFR:2377 tracer demonstrated specific high affinity (160±60 pM) binding to EGFR-expressing A431 epidermoid carcinoma cell line. In mice bearing A431 xenografts, 89Zr-DFO-ZEGFR:2377 demonstrated specific uptake in tumours and EGFR-expressing tissues. The tracer provided tumour uptake of 2.6±0.5% ID/g and tumour-to-blood ratio of 3.7±0.6 at 24 h after injection. 89Zr-DFO-ZEGFR:2377 provides higher tumour-to-organ ratios than anti-EGFR antibody 89Zr-DFO-cetuximab at 48 h after injection. EGFR‑expressing tumours were clearly visualized by microPET using 89Zr-DFO-ZEGFR:2377 at both 3 and 24 h after injection. In conclusion, 89Zr-DFO-ZEGFR:2377 is a potential probe for PET imaging of EGFR-expression in vivo.

Place, publisher, year, edition, pages
2016. Vol. 48, no 4, 1325-1332 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-286832DOI: 10.3892/ijo.2016.3369ISI: 000372567100002PubMedID: 26847636OAI: oai:DiVA.org:uu-286832DiVA: diva2:922064
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2016-04-21 Created: 2016-04-21 Last updated: 2016-04-27Bibliographically approved

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Garousi, JavadMitran, BogdanOrlova, AnnaTolmachev, Vladimir

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