title: Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging.
abstract: Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET) imaging have been synthesized and evaluated as diagnostic imaging probes for cancer characterization. Given that inhibitor coverage of the kinome is continuously expanding, in vivo PET imaging will likely find increasing applications for therapy monitoring and receptor density studies both in- and outside of oncological conditions. Early investigated radiolabeled inhibitors, which are mostly based on clinically approved tyrosine kinase inhibitor (TKI) isotopologues, have now entered clinical trials. Novel radioligands for cancer and PET neuroimaging originating from novel but relevant target kinases are currently being explored in preclinical studies. This article reviews the literature involving radiotracer design, radiochemistry approaches, biological tracer evaluation and nuclear imaging results of radiolabeled kinase inhibitors for PET reported between 2010 and mid-2015. Aspects regarding the usefulness of pursuing selective vs. promiscuous inhibitor scaffolds and the inherent challenges associated with intracellular enzyme imaging will be discussed.
authors.affiliation: Division of Oncological Imaging, Department of Oncology, University of Alberta, 11560 University Ave., Edmonton, AB T6G 1Z2, Canada. bernardg@ualberta.ca.
authors.forename: Vadim
authors.initials: V
authors.lastname: Bernard-Gauthier
authors.affiliation: Division of Oncological Imaging, Department of Oncology, University of Alberta, 11560 University Ave., Edmonton, AB T6G 1Z2, Canada. jjbailey@ualberta.ca.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Bailey
authors.affiliation: Division of Oncological Imaging, Department of Oncology, University of Alberta, 11560 University Ave., Edmonton, AB T6G 1Z2, Canada. sberke@ualberta.ca.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Berke
authors.affiliation: Division of Oncological Imaging, Department of Oncology, University of Alberta, 11560 University Ave., Edmonton, AB T6G 1Z2, Canada. schirrma@ualberta.ca.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics
chemical_list: D047428:Protein Kinase Inhibitors; D019275:Radiopharmaceuticals; D011505:Protein-Tyrosine Kinases
keywords: cancer imaging; carbon-11; fluorine-18; neuroimaging; nuclear imaging; positron emission tomography; protein kinases; tyrosine kinase inhibitors