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Affibody-mediated imaging of EGFR expression in prostate cancer using radiocobalt-labeled DOTA-Z(EGFR:2377)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, SE-10691 Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
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2019 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 41, no 1, p. 534-542Article in journal (Refereed) Published
Abstract [en]

The epidermal growth factor receptor (EGFR) is often overexpressed during prostate cancer (PCa) progression towards androgen-independence after hormone therapy, but the overexpression is lower than in other types of cancers. Despite the low expression, EGFR has emerged as a promising therapeutic target for patients with castration-resistant PCa. Non-invasive methods for determination of EGFR expression in PCa can serve for patient stratification and therapy response monitoring. Radionuclide imaging probes based on affibody molecules (7 kDa) provide high contrast imaging of cancer-associated molecular targets. We hypothesized that the anti-EGFR affibody molecule DOTA-Z(EGFR:2377) labeled with Co-55 (positron-emitter, T1/2=17.5 h) would enable imaging of EGFR expression in PCa xenografts. The human PCa cell line DU-145 was used for in vitro and in vivo experiments and Co-57 was used as a surrogate for Co-55 in the present study. Binding of Co-57-DOTA-Z(EGFR:2377) to EGFR-expressing xenografts was saturable with anti-EGFR monoclonal antibody cetuximab, which would motivate the use of this tracer for monitoring the receptor occupancy during treatment. A significant dose-dependent difference in radioactivity accumulation in tumors and normal organs was observed when the biodistribution was studied 3 h after the injection of 10 and 35 mu g of Co-57-DOTA-Z(EGFR:2377): At lower doses the tumor uptake was 2-fold higher although tumor-to-organ ratios were not altered. For clinically relevant organs for PCa, tumor-to-organ ratios increased with time, and at 24 h pi were 2.2 +/- 0.5 for colon, 7 +/- 2 for muscle, and 4.0 +/- 0.7 for bones. Small animal SPECT/CT images confirmed the capacity of radiocobalt labeled DOTA-Z(EGFR:2377) to visualize EGFR expression in PCa. In conclusion, the present study demonstrated the feasibility of using the radiocobalt labeled anti-EGFR affibody conjugate Z(EGFR:2377) as an imaging agent for in vivo visualization of low EGFR-expressing tumors, like PCa, and for monitoring of receptor occupancy during cetuximab therapy as well as the importance of optimal dosing in order to achieve higher sensitivity molecular imaging.

Place, publisher, year, edition, pages
2019. Vol. 41, no 1, p. 534-542
Keywords [en]
prostate cancer, molecular imaging, cobalt, affibody molecule, HER1, EGFR
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-372751DOI: 10.3892/or.2018.6792ISI: 000452152300051PubMedID: 30320363OAI: oai:DiVA.org:uu-372751DiVA, id: diva2:1278906
Funder
Swedish Research Council, 621-2012-5236Swedish Research Council, 2015-02509Swedish Research Council, 2015-02353VINNOVA, 2016-04060VINNOVA, 2017-02015Knut and Alice Wallenberg FoundationAvailable from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-15Bibliographically approved

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Mitran, BogdanLindström, ElinGarousi, JavadRosestedt, MariaTolmachev, VladimirOrlova, Anna

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