Synthesis and biodistribution of [18F]FE@CIT, a new potential tracer for the dopamine transporter
- Author(s)
- Markus Mitterhauser, Wolfgang Wadsak, Leonhard-Key Mien, Alexander Hoepping, Helmut Viernstein, Robert Dudczak, Kurt Kletter
- Abstract
In the last decade radiolabeled tropane analogs based on ß-CIT have proven indispensable for the imaging of the dopamine transporter. However, further improvements in their pharmacodynamic and pharmacokinetic features are desirable. An important improvement, yielding in higher affinity to the dopamine transporter (DAT) vs. serotonin transporter (SERT), can be achieved by a simple replacement of the carboxylic methyl ester group in ß-CIT by a fluoroethyl ester. The preparation and ex vivo evaluation of this new ß-CIT-analog ([18F]FE@CIT) is presented here. Precursor and standard were prepared from ß-CIT and analyzed by spectroscopic methods. Yields of precursor and standard preparation were 61% and 42%, respectively. [18F]FE@CIT was prepared by distillation of [18F]bromofluoroethane ([ 18F]BFE) and reaction with (1R-2-exo-3-exo)8-methyl-3-(4-iodo-phenyl) -8-azabicyclo[3.2.1] octane-2-carboxylic acid. After 10 min at 150°C the product was purified using a C-18 SepPak. The radiosynthesis evinced radiochemical yields of >90% (based on [18F]BFE), the specific radioactivity was >416 GBq/œmol. An average 30 œ.Ah cyclotron irradiation yielded more than 2.5 GBq [18F]FE@CIT. For the ex vivo bioevaluation, 20 male Sprague-Dawley rats were sacrificed at 5, 15, 30, 60, and 120 min after injection. Organs were removed, weighed, and counted. For autoradiographic experiments, transverse brain slices of about 100 œm were prepared. The ex vivo evaluation showed highest brain uptake in striatal regions, followed by thalamus and cerebellum. The highest striatum to cerebellum ratio was 3.73 and the highest thalamus to cerebellum ratio was 1.65. Autoradiographic images showed a good and differentiated uptake in striatal regions with a good target-to-background ratio. Œ 2004 Wiley-Liss, Inc.
- Organisation(s)
- Department of Inorganic Chemistry, Department of Sport and Human Movement Science
- External organisation(s)
- ABX - Advanced Biochemical Compounds
- Journal
- Synapse (New York)
- Volume
- 55
- Pages
- 73-79
- No. of pages
- 7
- ISSN
- 0887-4476
- Publication date
- 2005
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 3012 Pharmacy, Pharmacology, Toxicology
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/e68d74af-56d0-4be2-9f6b-9dd4000dce7b