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Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with Tc-99m using a peptide-based cysteine-containing chelator
KTH, School of Biotechnology (BIO), Protein Technology.
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2016 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 49, no 6, p. 2285-2293Article in journal (Refereed) Published
Abstract [en]

The epidermal growth factor receptor (EGFR) is overexpressed in a number of malignant tumors and is a molecular target for several specific anticancer antibodies and tyrosine kinase inhibitors. The overexpression of EGFR is a predictive biomarker for response to several therapy regimens. Radionuclide molecular imaging might enable detection of EGFR overexpression by a non-invasive procedure and could be used repeatedly. Affibody molecules are engineered scaffold proteins, which could be selected to have a high affinity and selectivity to predetermined targets. The anti-EGFR ZEGFR:2377 affibody molecule is a potential imaging probe for EGFR detection. The use of the generator-produced radionuclide Tc-99m should facilitate clinical translation of an imaging probe due to its low price, availability and favorable dosimetry of the radionuclide. In the present study, we evaluated feasibility of ZEGFR:2377 labeling with Tc-99m using a peptide-based cysteine-containing chelator expressed at the C-terminus of ZEGFR:2377. The label was stable in vitro under cysteine challenge. In addition, Tc-99m-ZEGFR:2377 was capable of specific binding to EGFR-expressing cells with high affinity (274 pM). Studies in BALB/C nu/nu mice bearing A431 xenografts demonstrated that Tc-99m-ZEGFR:2377 accumulates in tumors in an EGFR-specific manner. The tumor uptake values were 3.6 1 and 2.5 0.4% ID/g at 3 and 24 h after injection, respectively. The corresponding tumor-to-blood ratios were 1.8 0.4 and 8 3. The xenografts were clearly visualized at both time-points. This study demonstrated the potential of Tc-99m-labeled ZEGFR:2377 for imaging of EGFR in vivo.

Place, publisher, year, edition, pages
SPANDIDOS , 2016. Vol. 49, no 6, p. 2285-2293
Keywords [en]
epidermal growth factor receptor, radionuclide molecular imaging, affibody molecules, technetium-99m, A431, biodistribution
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:kth:diva-199524DOI: 10.3892/ijo.2016.3721ISI: 000389166000011Scopus ID: 2-s2.0-84996565692OAI: oai:DiVA.org:kth-199524DiVA, id: diva2:1065766
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QC 20170116

Available from: 2017-01-16 Created: 2017-01-09 Last updated: 2017-11-29Bibliographically approved

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Andersson, Ken G.Ståhl, StefanLöfblom, John

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