P-Glycoprotein (P-gp) is an efflux transporter widely expressed at the human blood-brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P-gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2-[2-(2-methyl-((11)C)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(11)C]-5); 2-[2-(2-fluoromethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinoline ([(18)F]-6); and 2-[2-(2-fluoroethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(18)F]-7), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P-gp. Methyl derivative [(11)C]-5 is a potent P-gp substrate, whereas the corresponding fluoroethyl derivative [(18)F]-7 is a P-gp inhibitor. Fluoromethyl compound [(18)F]-6 is classified as a non-transported P-gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [(11)C]-5 and [(18)F]-7, respectively, for in vivo imaging of P-gp by using PET.

11C- and 18F-Labeled Radioligands for P-Glycoprotein Imaging by Positron Emission Tomography

Cantore, M
;
COLABUFO, Nicola Antonio;
2016-01-01

Abstract

P-Glycoprotein (P-gp) is an efflux transporter widely expressed at the human blood-brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P-gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2-[2-(2-methyl-((11)C)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(11)C]-5); 2-[2-(2-fluoromethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinoline ([(18)F]-6); and 2-[2-(2-fluoroethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(18)F]-7), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P-gp. Methyl derivative [(11)C]-5 is a potent P-gp substrate, whereas the corresponding fluoroethyl derivative [(18)F]-7 is a P-gp inhibitor. Fluoromethyl compound [(18)F]-6 is classified as a non-transported P-gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [(11)C]-5 and [(18)F]-7, respectively, for in vivo imaging of P-gp by using PET.
File in questo prodotto:
File Dimensione Formato  
ChemMedChem 2016,11, 108-118 (131).pdf

non disponibili

Tipologia: Documento in Versione Editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.34 MB
Formato Adobe PDF
1.34 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/147808
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact