Bolcaen, JulieNair, ShankariDriver, Cathryn H.S.Vandevoorde, CharlotBoshomane, Tebatso M.G.Ebenhan, ThomasVandevoorde, Charlot2022-02-282022-02-282021-06Bolcaen, J.; Nair, S.; Driver, C.H.S.; Boshomane, T.M.G.; Ebenhan, T.; Vandevoorde, C. Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma. Pharmaceuticals 2021, 14, 626. https://doi.org/10.3390/ph14070626.1424-8247 (online)10.3390/ ph14070626http://hdl.handle.net/2263/84248Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.en© 2021 by the authors. Licensee: MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Targeted radionuclide therapyGlioblastomaRadiochemistryTheranosticsMolecular imagingTyrosine kinasesRadiopharmaceuticalsReceptor tyrosine kinase inhibitor (RTKI)Article