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Molecular Imaging and Biology

, Volume 18, Issue 6, pp 916–923 | Cite as

Synthesis and In Vivo Imaging of N-(3-[11C]Methoxybenzyl)-2-(3-Methoxyphenyl)ethylaniline as a Potential Targeting Agent for P-glycoprotein

  • Debora Petroni
  • Antonietta Bartoli
  • Simona Rapposelli
  • Maria Digiacomo
  • Silvia Burchielli
  • Giulia Nesi
  • Annalina Lapucci
  • Silvia Pardini
  • Sabrina Fucci
  • Marco Macchia
  • Piero A. Salvadori
  • Luca Menichetti
Research Article
  • 202 Downloads

Abstract

Purpose

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.

Procedures

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).

Results

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.

Conclusions

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.

Key words

P-glycoprotein Multidrug resistance CNS radiotracers [11C]-Methylation Arylethylphenylamine derivatives Arylethylphenoxy derivatives Pgp inhibitor Tariquidar 

Notes

Acknowledgments

This study was partially supported by the grant PRIN2009 (20097FJHPZ_003) from the Ministero dell’Istruzione dell’Università e della Ricerca (MIUR) Italy.

Compliance with Ethical Standards

The experimental protocol, which conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85–23, revised 1996), was approved by the Animal Care Committee of the Italian Ministry of Health (protocol no. 0000249/2014).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© World Molecular Imaging Society 2016

Authors and Affiliations

  • Debora Petroni
    • 1
  • Antonietta Bartoli
    • 2
  • Simona Rapposelli
    • 3
  • Maria Digiacomo
    • 3
  • Silvia Burchielli
    • 4
  • Giulia Nesi
    • 3
  • Annalina Lapucci
    • 3
  • Silvia Pardini
    • 1
  • Sabrina Fucci
    • 4
  • Marco Macchia
    • 3
  • Piero A. Salvadori
    • 1
  • Luca Menichetti
    • 1
  1. 1.Institute of Clinical PhysiologyConsiglio Nazionale delle Ricerche (CNR)PisaItaly
  2. 2.Molecular Imaging CentreUniversity of TurinIvreaItaly
  3. 3.Department of PharmacyUniversity of PisaPisaItaly
  4. 4.Fondazione Toscana G. MonasterioPisaItaly

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