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The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
KTH Royal Inst Technol, Dept Prot Technol.
Odense Univ Hosp, Dept Nucl Med.ORCID iD: 0000-0001-6577-7011
Odense Univ Hosp, Dept Nucl Med..
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 5961Article in journal (Refereed) Published
Abstract [en]

Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The In-111-labelled DOTA-conjugated Z(EGFR:2377) Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-Z(EGFR:2377). DOTA-Z(EGFR:2377) was labelled with Co-57 (T-1/2 = 271.8 d), Co-55 (T-1/2 = 17.5 h), and, for comparison, with the positron-emitting radionuclide Ga-68 (T-1/2 = 67.6 min) with preserved specificity of binding to EGFR-expressing A431 cells. The long-lived cobalt radioisotope Co-57 was used in animal studies. Both Co-57-DOTA-Z(EGFR:2377) and Ga-68-DOTA-Z(EGFR:2377) demonstrated EGFR-specific accumulation in A431 xenografts and EGFR-expressing tissues in mice. Tumour-to-organ ratios for the radiocobalt-labelled DOTA-Z(EGFR:2377) were significantly higher than for the gallium-labelled counterpart already at 3 h after injection. Importantly, Co-57-DOTA-Z(EGFR:2377) demonstrated a tumour-to-liver ratio of 3, which is 7-fold higher than the tumour-to-liver ratio for (68)GaDOTA-Z(EGFR:2377). The results of this study suggest that the positron-emitting cobalt isotope 55Co would be an optimal label for DOTA-Z(EGFR:2377) and further development should concentrate on this radionuclide as a label.

Place, publisher, year, edition, pages
2017. Vol. 7, article id 5961
Keywords [en]
Epidermal-Growth-Factor; Factor Receptor Expression; Cell Lung-Cancer; Monoclonal-Antibody; Integrin Expression; Somatostatin Analog; Quantitative Pet; Positive Tumors; Carcinoma; Head
National Category
Cancer and Oncology Immunology in the medical area
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URN: urn:nbn:se:uu:diva-334098DOI: 10.1038/s41598-017-05700-7ISI: 000405907800015PubMedID: 28729680OAI: oai:DiVA.org:uu-334098DiVA, id: diva2:1159051
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-01-13Bibliographically approved

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Garousi, JavadDam, Johan H.Mitran, BogdanOrlova, AnnaBuijs, JosTolmachev, Vladimir
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