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.
|Radiosynthesis and in vitro autoradiographic image in the brain of a CD1 mouse of the distribution of 18F-labelled fluoro-indiplon.|
H. Lundbeck A/S, Copenhagen, Denmark
Department of Neurology, Universität Leipzig, Germany
Advanced Biochemical Compounds ABX GmbH, Radeberg, Germany
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Financial Support by
- European Regional Development Fund