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Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
CNR, Inst Biostruct & Bioimaging, Naples, Italy..
CNR, Inst Biostruct & Bioimaging, Naples, Italy..
CNR, Inst Biostruct & Bioimaging, Naples, Italy..
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 2998Article in journal (Refereed) Published
Abstract [en]

HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabeled low molecular weight peptide ligands are particularly attractive as probes for molecular imaging, since they reach and bind to the target and clear from non-target organs and blood stream faster than bulky antibodies. In this study, we evaluated a potential HER2-imaging probe, an A9 nonapeptide, derived from the trastuzumab-Fab portion. Its cellular uptake was investigated by mass spectrometry analysis of the cytoplasmic cellular extracts. Moreover, based on in-silico modeling, DTPA chelator was conjugated to N-terminus of A9. In-111-labeled A9 demonstrated nanomolar affinity to HER2-expressing BT474 cells and favorable biodistribution profile in NMRI mice. This study suggests that the peptide A9 represents a good lead candidate for development of molecular probe, to be used for imaging purposes and for the delivery of cytotoxic agents.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 8, article id 2998
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
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URN: urn:nbn:se:uu:diva-348106DOI: 10.1038/s41598-018-21283-3ISI: 000424985800036PubMedID: 29445216OAI: oai:DiVA.org:uu-348106DiVA, id: diva2:1196883
Funder
Swedish Cancer Society, CAN 2015/350Swedish Research Council, 2015-02353Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-04-11Bibliographically approved

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