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Radiolabeled Probes Targeting Tyrosine-Kinase Receptors For Personalized Medicine
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.ORCID iD: 0000-0001-6120-2683
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
2014 (English)In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 20, no 14, 2275-2292 p.Article in journal (Refereed) Published
Abstract [en]

Receptor tyrosine kinases (RTK) are transmembrane receptors regulating cellular proliferation, differentiation, apoptosis, motility and recruitment of the vasculature. Aberrant expression and/or function of RTK have been detected in many malignant tumors and are considered to be a part of the transformed phenotype. The action of several classes of anti-cancer drugs is based on specific recognition of RTK. Monoclonal antibodies target extracellular binding domains, while tyrosine kinase inhibitors (TKI) bind to intracellular kinase domains to suppress RTK signaling. The issues regarding the efficient use of RTK targeting are the inter- and intra-patient heterogeneity of RTK expression and the changes of expression levels during the course of disease and in response to therapy. Radionuclide molecular imaging of RTK expression may aid in selecting patients who would benefit from RTK-targeting therapy and in identifying non-responders. Therefore, the therapy would be more personalized. Currently, radiolabeled proteins (monoclonal antibodies and their fragments, natural peptides ligands to RTK and de novo selected affinity proteins) and TKI and their analogues are under development for the visualization of RTK. In this review, we discuss the advantages and disadvantages of these approaches.

Place, publisher, year, edition, pages
2014. Vol. 20, no 14, 2275-2292 p.
Keyword [en]
Radionuclide, molecular imaging, receptor tyrosine kinases, monoclonal antibodies, tyrosine kinase inhibitors, scaffold proteins
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-227887DOI: 10.2174/13816128113196660667ISI: 000336168400005OAI: oai:DiVA.org:uu-227887DiVA: diva2:731754
Available from: 2014-07-02 Created: 2014-07-01 Last updated: 2017-12-05Bibliographically approved

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Altai, MohamedOrlova, AnnaTolmachev, Vladimir

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