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PET imaging of epidermal growth factor receptor expression in tumours using Zr-89-labelled ZEGFR:2377 affibody molecules
KTH, School of Biotechnology (BIO), Protein Technology.
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2016 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 48, no 4, 1325-1332 p.Article in journal (Refereed) PublishedText
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 radionuclide Zr-89. The Zr-89-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, Zr-89-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. Zr-89-DFO-ZEGFR: 2377 provides higher tumour-to-organ ratios than anti-EGFR antibody Zr-89-DFO-cetuximab at 48 h after injection. EGFR-expressing tumours were clearly visualized by microPET using Zr-89-DFO-ZEGFR: 2377 at both 3 and 24 h after injection. In conclusion, Zr-89-DFO-ZEGFR: 2377 is a potential probe for PET imaging of EGFR-expression in vivo.

Place, publisher, year, edition, pages
Spandidos , 2016. Vol. 48, no 4, 1325-1332 p.
Keyword [en]
epidermal growth factor receptor, affibody molecules, radionuclide imaging, positron emission tomography, zirconium-89, xenografts
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:kth:diva-185347DOI: 10.3892/ijo.2016.3369ISI: 000372567100002ScopusID: 2-s2.0-84959020465OAI: oai:DiVA.org:kth-185347DiVA: diva2:921800
Funder
Swedish Research CouncilSwedish Cancer Society
Note

QC 20160421

Available from: 2016-04-21 Created: 2016-04-18 Last updated: 2016-04-21Bibliographically approved

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Anderson, Ken G.Ståhl, StefanLöfblom, John
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