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Preclinical Evaluation of [Ga-68]Ga-DFO-ZEGFR:2377: A Promising Affibody-Based Probe for Noninvasive PET Imaging of EGFR Expression in Tumors
Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden..
Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.ORCID iD: 0000-0001-9423-0541
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2018 (English)In: CELLS, ISSN 2073-4409, Vol. 7, no 9, article id 141Article in journal (Refereed) Published
Abstract [en]

Radionuclide imaging of epidermal growth factor receptor (EGFR) expression in tumors may stratify patients for EGFR-targeting therapies and predict response or resistance to certain treatments. Affibody molecules, which are nonimmunoglobulin scaffold proteins, have a high potential as probes for molecular imaging. In this study, maleimido derivative of desferrioxamine B (DFO) chelator was site-specifically coupled to the C-terminal cysteine of the anti-EGFR affibody molecule ZEGFR:2377, and the DFO-ZEGFR:2377 conjugate was labeled with the generator-produced positron-emitting radionuclide Ga-68. Stability, specificity of binding to EGFR-expressing cells, and processing of [Ga-68]Ga-DFO-ZEGFR:2377 by cancer cells after binding were evaluated in vitro. In vivo studies were performed in nude mice bearing human EGFR-expressing A431 epidermoid cancer xenografts. The biodistribution of [Ga-68]Ga-DFO-ZEGFR:2377 was directly compared with the biodistribution of [Zr-89]Zr-DFO-ZEGFR:2377. DFO-ZEGFR:2377 was efficiently (isolated yield of 73 +/- 3%) and stably labeled with Ga-68. Binding of [Ga-68]Ga-DFO-ZEGFR:2377 to EGFR-expressing cells in vitro was receptor-specific and proportional to the EGFR expression level. In vivo saturation experiment demonstrated EGFR-specific accumulation of [Ga-68]Ga-DFO-ZEGFR:2377 in A431 xenografts. Compared to [Zr-89]Zr-DFO-ZEGFR:2377, [Ga-68]Ga-DFO-ZEGFR:2377 demonstrated significantly (p < 0.05) higher uptake in tumors and lower uptake in spleen and bones. This resulted in significantly higher tumor-to-organ ratios for [Ga-68]Ga-DFO-ZEGFR:2377. In conclusion, [Ga-68]Ga-DFO-ZEGFR:2377 is a promising probe for imaging of EGFR expression.

Place, publisher, year, edition, pages
MDPI, 2018. Vol. 7, no 9, article id 141
Keywords [en]
EGFR, radionuclide imaging, PET, affibody molecules, Ga-68, Zr-89, DFO, nude mice, A431 xenografts
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-239116DOI: 10.3390/cells7090141ISI: 000448332400028PubMedID: 30231504OAI: oai:DiVA.org:kth-239116DiVA, id: diva2:1264522
Funder
Swedish Cancer Society, CAN 2015/350 2017/649 2017/425Vinnova, 2016-04060Swedish Research Council, 2015-02353 2015-02509
Note

QC 20181120

Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2019-08-20Bibliographically approved

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Andersson, Ken G.Löfblom, John

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