Affibody-mediated PET imaging of HER3 expression in malignant tumours
2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 15226Article in journal (Refereed) Published
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
Medical Image Processing Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-266695DOI: 10.1038/srep15226ISI: 000362985400001PubMedID: 26477646OAI: oai:DiVA.org:uu-266695DiVA: diva2:868897
FunderSwedish Cancer SocietySwedish Research Council