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

Mariangela Cantore*, Marcel Benadiba, Philippus Elsinga, Chantal Kwizera, Rudi Dierckx, Nicola A. Colabufo, Geert Luurtsema

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
1 Downloads (Pure)

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-(C-11)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([C-11]-5); 2-[2-(2-fluoromethyl-(F-18)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinoline ([F-18]-6); and 2-[2-(2-fluoroethyl-(F-18)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([F-18]-7), were tested in several invitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P-gp. Methyl derivative [C-11]-5 is a potent P-gp substrate, whereas the corresponding fluoroethyl derivative [F-18]-7 is a P-gp inhibitor. Fluoromethyl compound [F-18]-6 is classified as a non-transported P-gp substrate, because its efflux increases after cyclosporineA modulation. These studies revealed a promising substrate and inhibitor, [C-11]-5 and [F-18]-7, respectively, for invivo imaging of P-gp by using PET.

Original languageEnglish
Pages (from-to)108-118
Number of pages11
JournalChemMedChem
Volume11
Issue number1
DOIs
Publication statusPublished - 5-Jan-2016

Keywords

  • glycoproteins
  • inhibitors
  • isotope labeling
  • positron emission tomography
  • radioligands
  • BLOOD-BRAIN-BARRIER
  • CANCER RESISTANCE PROTEIN
  • IN-VITRO
  • NEURODEGENERATIVE DISEASE
  • PRECLINICAL EVALUATION
  • INHIBITION
  • TRACER
  • ASSAYS
  • PET
  • DERIVATIVES

Cite this