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Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR: 2377 affibody molecule labeled with 99mTc using a peptide-based cysteine-containing chelator
KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, Sweden.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap. (Vladimir Tolmachev)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap. (Vladimir Tolmachev)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning. (Anna Orlova)
Vise andre og tillknytning
2016 (engelsk)Inngår i: International journal of oncology, ISSN 1791-2423, Vol. 49, nr 6, s. 2285-2293Artikkel i tidsskrift (Fagfellevurdert) 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 99mTc 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 99mTc 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, 99mTc-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 99mTc-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 99mTc-labeled ZEGFR:2377 for imaging of EGFR in vivo.

sted, utgiver, år, opplag, sider
2016. Vol. 49, nr 6, s. 2285-2293
Emneord [en]
epidermal growth factor receptor, radionuclide molecular imaging, affibody molecules, technetium-99m, A431, biodistribution
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-312073DOI: 10.3892/ijo.2016.3721ISI: 000389166000011PubMedID: 27748899OAI: oai:DiVA.org:uu-312073DiVA, id: diva2:1062148
Forskningsfinansiär
Swedish Cancer SocietySwedish Research Council
Merknad

Equal contribution of Andersson and Oroujeni

Tilgjengelig fra: 2017-01-04 Laget: 2017-01-04 Sist oppdatert: 2018-01-13bibliografisk kontrollert

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