title: PET Tracers for Imaging of ABC Transporters at the Blood-Brain Barrier: Principles and Strategies.
abstract: ABC transporters at the human blood-brain barrier protect the brain against the entry of harmful compounds but may also limit (or prevent) the cerebral entry of therapeutic drugs (e.g. anti-epileptics, antidepressants and antipsychotics). The efflux function of these transporters may be impaired in neurodegenerative disorders like Alzheimer and Parkinson disease. For such reasons, there is much interest in modulation of the efflux function of ABC transporters and in the monitoring of this function with positron emission tomography (PET). The efflux function of P-glycoprotein, an important member of the ABC transporter family, can be quantified with the PET tracer (R)-[11C]verapamil, but the lipophilicity of this probe and the formation of radioactive metabolites which enter the brain complicate such measurements considerably. (R)-[11C]verapamil is also not very suitable for the detection of P-gp upregulation, as may occur in epilepsy or drug resistance. Current radiochemical efforts are therefore focused on the development of PET probes with improved characteristics, for example; capability to detect both up- and down regulation of transporter function and expression, a better metabolic profile (no brain-entering metabolites), reduced lipophilicity and a longer physical half-life (labeling with 18F instead of 11C).
authors: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Hanzeplein 1, 9713GZ, Groningen, the Netherlands.
authors: Gert
authors: G
authors: Luurtsema
authors: Philip
authors: P
authors: Elsinga
authors: Rudi
authors: R
authors: Dierckx
authors: Ronald
authors: R
authors: Boellaard
authors: Aren
authors: A
authors: van Waarde
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers
chemical_list: D018528:ATP-Binding Cassette Transporters; D011849:Radioactive Tracers