Contact

Porträt Prof. Dr. Brust, Peter; FWPN

Prof. Dr. Peter Brust
Head
p.brustAthzdr.de
Phone: +49 351 260 - 4610
Fax: +49 351 260 - 4699

Pharmacology and PET-imaging properties of fluorinated derivatives of GABAA receptor ligands


To investigate the pharmacological properties at GABAA receptors and to promote the development of α1 subunit selective radiotracers for positron emission tomography imaging, we designed and evaluated various fluorinated indiplon derivatives. In vitro studies indicated an α1 preference of all newly synthesized indiplon derivatives. The radiosynthesis of [18F]fluoro-indiplon was performed using the bromoacetyl precursor followed by multiple-stage purification using semipreparative HPLC and solid phase extraction. Stability, partition coefficients, binding affinities and regional brain binding were determined in vitro. Biodistribution and radiotracer metabolism were assessed in biodistribution studies in mice.

FWPN GABA
Radiosynthesis and in vitro autoradiographic image in the brain of a CD1 mouse of the distribution of 18F-labelled fluoro-indiplon.

Partner

  • H. Lundbeck A/S, Copenhagen, Denmark

  • Department of Neurology, Universität Leipzig, Germany

  • Advanced Biochemical Compounds ABX GmbH, Radeberg, Germany

Publications

  • Deuther-Conrad W, Fischer S, Scheunemann M, Hiller A, Diekers M, Friemel A, Wegner F, Steinbach J, Hoepping A, Brust P. GABAA receptor specific pyrazolopyrimidines as potential imaging agents: In vivo characteristics of a new 18F-labelled indiplon derivative. Curr. Radiopharm. 2009, 2, 24-31

  • Wegner F, Deuther-Conrad W, Scheunemann M, Brust P, Fischer S, Hiller A, Diekers M, Strecker K, Wohlfarth K, Allgaier C, Steinbach J, Hoepping A. GABAA receptor pharmacology of fluorinated derivatives of the novel sedative-hypnotic pyrazolopyrimidine indiplon. Eur J Pharmacol. 2008,580(1-2):1-11.

  • Fischer S, Hiller A, Scheunemann M, Deuther-Conrad W, Hoepping A, Diekers M, Wegner F, Brust P, Steinbach J. Radiosynthesis of novel 18F labelled derivatives of indiplon as potential GABAA receptor imaging tracers for PET. J Label. Compd. Radiopharm. 2008, 51, 123-131.
  • Hoepping A, Diekers M, Deuther-Conrad W, Scheunemann M, Fischer S, Hiller A, Wegner F, Steinbach J, Brust P. Synthesis of fluorine substituted pyrazolopyrimidines as potential leads for the development of PET-imaging agents for the GABAA receptors. Bioorg Med Chem. 2008,16(3):1184-94.

  • Friemel A, Ebert B, Hutson PH, Brust P, Nieber K, Deuther-Conrad W. Postnatal development and kinetics of [3H]gaboxadol binding in rat brain: in vitro homogenate binding and quantitative autoradiography.Brain Res. 2007,1170:39-47.

  • Hoepping A, Scheunemann M, Fischer S, Deuther-Conrad W, Hiller A, Wegner F, Diekers M, Steinbach J, Brust P.Radiosynthesis and biological evaluation of an 18F-labeled derivative of the novel pyrazolopyrimidine sedative-hypnotic agent indiplon. Nucl Med Biol. 2007,34(5):559-70.  

Financial Support by

  • European Regional Development Fund

Contact

Prof. Dr. Peter Brust
Head
p.brustAthzdr.de
Phone: +49 351 260 - 4610
Fax: +49 351 260 - 4699