English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

P-glycoprotein is an efflux transporter located in the blood-brain barrier. (R)-[ 11 C]Verapamil is widely used as a PET tracer to investigate its function in patients with epilepsy, Alzheimer's disease, and other neurodegenerative diseases. Currently it is not possible to use this successful tracer in clinics without a cyclotron, because of the short half-life of carbon-11. We developed two new fluorine-18 labeled (R)-verapamil analogs, with the benefit of a longer half-life. The synthesis of (R)-N-[ 18 F]fluoroethylverapamil ([ 18 F]1) and (R)-O-[ 18 F]fluoroethylnorverapamil ([ 18 F]2) has been described. [ 18 F]1 was obtained in reaction of (R)-norverapamil with the volatile [ 18 F]fluoroethyltriflate acquired from bromoethyltosylate and a silver trilate column with a radiochemical yield of 2.7% ± 1.2%. [ 18 F]2 was radiolabeled by direct fluorination of precursor 13 and required final Boc-deprotection with TFA resulting in a radiochemical yield of 17.2% ± 9.9%. Both tracers, [ 18 F]1 and [ 18 F]2, were administered to Wistar rats, and blood plasma and brain samples were analyzed for metabolic stability. Using [ 18 F]1 and [ 18 F]2, PET scans were performed in Wistar rats at baseline and after blocking with tariquidar, showing a 3.6- and 2.4-fold increase in brain uptake in the blocked rats, respectively. In addition, for both [ 18 F]1 and [ 18 F]2, PET scans in Mdr1a/b (-/-) , Bcrp1 (-/-) , and WT mice were acquired, in which [ 18 F]2 showed a more specific brain uptake in Mdr1a/b (-/-) mice and no increased signal in Bcrp1 (-/-) mice. [ 18 F]2 was selected as the best performing tracer and should be evaluated further in clinical studies.

Synthesis and Evaluation of New Fluorine-18 Labeled Verapamil Analogs To Investigate the Function of P-Glycoprotein in the Blood–Brain Barrier