Radiolabeled Probes Targeting Tyrosine-Kinase Receptors For Personalized Medicine
Mohamed Altai, Anna Orlova and Vladimir Tolmachev
Pages 2275-2292 (18)
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.
Radionuclide, molecular imaging, receptor tyrosine kinases, monoclonal antibodies, tyrosine kinase inhibitors, scaffold proteins.
Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 81 Uppsala, Sweden.