title: Synthesis and In Vivo Imaging of N-(3-[11C]Methoxybenzyl)-2-(3-Methoxyphenyl)ethylaniline as a Potential Targeting Agent for P-glycoprotein.
abstract: The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistance and in the onset of neurodegenerative disease. Its function and most mechanisms of action are still under investigation. We developed a C-11-labeled 2-arylethylphenylamine-([11C]AEPH) derivative for positron emission tomography (PET), as a novel probe to better understand the activity and the function of Pgp in vivo.
  
  
  
  The synthetic procedure and the quality control of the selected lead compound, [11C]AEPH-1, were set up and optimized. The biodistribution and the dynamic extraction in target organs of [11C]AEPH-1 were studied in vivo by PET in healthy rats at baseline and after pre-treatment with a Pgp inhibitor (tariquidar).
  
  
  
  In vivo dynamic imaging was consistent with the results of ex vivo extraction on explanted organs. An adequate stability for in vivo studies, as well as a high activity of [11C]AEPH-1 in intestine and barrier tissues, has been demonstrated. Results of the blockade study showed a decrease of uptake after the pre-treatment, indicating a behavior attributable to a Pgp ligand.
  
  
  
  The suitable pharmacokinetics and the specificity tested in the pre-treated animals have indicated the potentiality of this AEPH derivative to act as Pgp ligand, providing new opportunities for further studies on expression and function of this important efflux transporter in the fields of neurology and oncology.
authors.affiliation: Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Via Moruzzi, 1, I-56124, Pisa, Italy. debora.petroni@ifc.cnr.it.
authors.forename: Debora
authors.initials: D
authors.lastname: Petroni
authors.affiliation: Molecular Imaging Centre, University of Turin, Via Nizza, 52, I-10125, Ivrea, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Bartoli
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno 6, I-56126, Pisa, Italy. simona.rapposelli@farm.unipi.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno 6, I-56126, Pisa, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Digiacomo
authors.affiliation: Fondazione Toscana G. Monasterio, Via Moruzzi, 1, I-56124, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Burchielli
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno 6, I-56126, Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Nesi
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno 6, I-56126, Pisa, Italy.
authors.forename: Annalina
authors.initials: A
authors.lastname: Lapucci
authors.affiliation: Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Via Moruzzi, 1, I-56124, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pardini
authors.affiliation: Fondazione Toscana G. Monasterio, Via Moruzzi, 1, I-56124, Pisa, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fucci
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno 6, I-56126, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.affiliation: Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Via Moruzzi, 1, I-56124, Pisa, Italy.
authors.forename: Piero A
authors.initials: PA
authors.lastname: Salvadori
authors.affiliation: Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Via Moruzzi, 1, I-56124, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Menichetti
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D000818:Animals; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000814:Aniline Compounds; C000623324:N-(3-methoxybenzyl)-2-(3-methoxyphenyl)ethylaniline
keywords: Arylethylphenoxy derivatives; Arylethylphenylamine derivatives; CNS radiotracers; Multidrug resistance; P-glycoprotein; Pgp inhibitor; Tariquidar; [11C]-Methylation