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Journal of Radioanalytical and Nuclear Chemistry

, Volume 322, Issue 2, pp 847–851 | Cite as

Radiolabeling and in vivo evaluation of [11C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT7 receptor

  • Elina T. L’Estrade
  • Ida N. Petersen
  • Mengfei Xiong
  • Adam S. Hogendorf
  • Agata Hogendorf
  • Jesper L. Kristensen
  • Andreas Kjær
  • Andrzej J. Bojarski
  • Maria Erlandsson
  • Tomas Ohlsson
  • Gitte M. Knudsen
  • Matthias M. HerthEmail author
Article
  • 41 Downloads

Abstract

AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT7R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT7R selective positron emission tomography (PET) tracer. 11C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [11C]AGH-44 displays low blood–brain-barrier passage in Long–Evans rats. Moreover, [11C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT7R selective PET tracer.

Keywords

AGH-44 5-HT7 PET Carbon-11 

Notes

Acknowledgements

The authors wish to thank the staff at the PET and Cyclotron unit for expert technical assistance.

Supplementary material

10967_2019_6687_MOESM1_ESM.docx (1001 kb)
Supplementary material 1 (DOCX 1000 kb)

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Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2019

Authors and Affiliations

  • Elina T. L’Estrade
    • 1
    • 2
    • 3
  • Ida N. Petersen
    • 4
    • 5
  • Mengfei Xiong
    • 1
    • 2
  • Adam S. Hogendorf
    • 6
  • Agata Hogendorf
    • 6
  • Jesper L. Kristensen
    • 2
  • Andreas Kjær
    • 4
    • 5
  • Andrzej J. Bojarski
    • 6
  • Maria Erlandsson
    • 3
  • Tomas Ohlsson
    • 3
  • Gitte M. Knudsen
    • 1
  • Matthias M. Herth
    • 1
    • 2
    • 4
    Email author
  1. 1.Neurobiology Research UnitRigshospitaletCopenhagenDenmark
  2. 2.Department for Drug Design and Pharmacology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  3. 3.Radiation Physics, Nuclear Medicine Physics UnitSkånes University HospitalLundSweden
  4. 4.Department of Clinical Physiology, Nuclear Medicine and PETUniversity Hospital Copenhagen, RigshospitaletCopenhagenDenmark
  5. 5.Cluster for Molecular Imaging, Faculty of Health ScienceUniversity of CopenhagenCopenhagenDenmark
  6. 6.Institute of PharmacologyPolish Academy of SciencesKrakówPoland

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