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Affibody-mediated PET imaging of HER3 expression in malignant tumours
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5Article in journal (Refereed) PublishedText
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 68Ga-labeled affibody molecules. The anti-HER3 affibody molecule HEHEHE-Z08698-NOTA was successfully labelled with 68Ga 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 68Ga-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 68Ga-HEHEHE-Z08698-NOTA shortly after administration.

Place, publisher, year, edition, pages
2015. Vol. 5
National Category
Radiology, Nuclear Medicine and Medical Imaging
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URN: urn:nbn:se:kth:diva-181983DOI: 10.1038/srep15226ISI: 000362985400001ScopusID: 2-s2.0-84945176046OAI: oai:DiVA.org:kth-181983DiVA: diva2:903192
Funder
Swedish Cancer SocietySwedish Research Council
Note

QC 20160215

Available from: 2016-02-15 Created: 2016-02-11 Last updated: 2016-02-15Bibliographically approved

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