Radiofluorinated N-Octanoyl Dopamine ([18F]F-NOD) as a Tool To Study Tissue Distribution and Elimination of NOD in Vitro and in Vivo

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Marc Pretze - , Heidelberg University  (Author)
  • Prama Pallavi - , Mannheim University of Applied Sciences (Author)
  • Mareike Roscher - (Author)
  • Sarah Klotz - (Author)
  • Julio Caballero - , Center for Bioinformatics and Molecular Simulations (Author)
  • Uta Binzen - (Author)
  • Wolfgang Greffrath - (Author)
  • Rolf-Detlef Treede - (Author)
  • Martin C Harmsen - , University of Groningen (Author)
  • Mathias Hafner - , Mannheim University of Applied Sciences (Author)
  • Benito Yard - (Author)
  • Carmen Wängler - (Author)
  • Björn Wängler - (Author)

Abstract

To mitigate pretransplantation injury in organs of potential donors, N-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in braindead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [18F]F-NOD [18F]5 for in vivo assessment of NOD's elimination kinetics by means of PET imaging. [18F]5 was synthesized in reproducibly high radiochemical yields and purity (>98%) as well as high specific activities (>20 GBq/μmol). Stability tests showed no decomposition of [18F]5 over a period of 120 min in rat plasma. In vitro, low cell association was found for [18F]5, indicating no active transport mechanism into cells. In vivo, [18F]5 exhibited a fast blood clearance and a predominant hepatobiliary elimination. As these data suggest that also NOD might be cleared fast, further pharmacokinetic evaluation is warranted.

Details

Original languageEnglish
Pages (from-to)9855-9865
Number of pages11
JournalJournal of medicinal chemistry
Volume59
Issue number21
Publication statusPublished - 10 Nov 2016
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 84994908330
ORCID /0000-0002-6432-5694/work/146644243

Keywords

Keywords

  • Animals, Cells, Cultured, Dopamine/analogs & derivatives, Fluorine Radioisotopes, HEK293 Cells, Humans, Molecular Structure, Positron-Emission Tomography, Rats, Rats, Inbred Lew, Tissue Distribution

Library keywords