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Affibody-mediated PET imaging of HER3 expression in malignant tumours
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
KTH Royal Inst Technol, Div Prot Technol, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 15226Article in journal (Refereed) Published
Abstract [en]

Human epidermal growth factor receptor 3 (HER3) is involved in the progression of various cancers and in resistance to therapies targeting the HER family. In vivo imaging of HER3 expression would enable patient stratification for anti-HER3 immunotherapy. Key challenges with HER3-targeting are the relatively low expression in HER3-positive tumours and HER3 expression in normal tissues. The use of positron-emission tomography (PET) provides advantages of high resolution, sensitivity and quantification accuracy compared to SPECT. Affibody molecules, imaging probes based on a non-immunoglobulin scaffold, provide high imaging contrast shortly after injection. The aim of this study was to evaluate feasibility of PET imaging of HER3 expression using Ga-68-labeled affibody molecules. The anti-HER3 affibody molecule HEHEHE-Z08698-NOTA was successfully labelled with Ga-68 with high yield, purity and stability. The agent bound specifically to HER3-expressing cancer cells in vitro and in vivo. At 3 h pi, uptake of Ga-68-HEHEHE-Z08698-NOTA was significantly higher in xenografts with high HER3 expression (BT474, BxPC-3) than in xenografts with low HER3 expression (A431). In xenografts with high expression, tumour-to-blood ratios were >20, tumour-to-muscle >15, and tumour-to-bone >7. HER3-positive xenografts were visualised using microPET 3 h pi. In conclusion, PET imaging of HER3 expression is feasible using Ga-68-HEHEHE-Z08698-NOTA shortly after administration.

Place, publisher, year, edition, pages
2015. Vol. 5, 15226
National Category
Medical Image Processing Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-266695DOI: 10.1038/srep15226ISI: 000362985400001PubMedID: 26477646OAI: oai:DiVA.org:uu-266695DiVA: diva2:868897
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2015-11-12 Created: 2015-11-10 Last updated: 2017-12-01Bibliographically approved

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