Synthesis and evaluation of 18F-labeled dopamine D3 receptor ligands as potential PET imaging agents.
A series of fluoro substituted aryl carboxamides was synthesized revealing high affinity for the dopamine D3 receptor. In contrast to 2-methoxy substitution, a 2,3-dichloro substitution pattern at the phenylpiperazine moiety induces a 10-fold increase of D3 affinity which is expressed by Ki values of 0.53, 1.1, and 9.0 nM for 8b, 8d, and 8f. Applying aromatic 18F-for-Br(Cl) substitution, high radiochemical yields between 76-82% were obtained for [18F]8c-f. The most promising ligand, [18F]8d, was used as imaging agent of the D3 receptor in vitro. However, due to the lack of specific binding, further studies should aim at the development of radioligands with improved D3 receptor selectivity.
Hocke
Carsten
C
Department of Nuclear Medicine, Krankenhausstrasse 12, D-91054 Erlangen, Germany. Carsten.Hocke@nuklear.imed.uni-erlangen.de
Prante
Olaf
O
Löber
Stefan
S
Hübner
Harald
H
Gmeiner
Peter
P
Kuwert
Torsten
T
D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis; D005462:Fluorine Radioisotopes; D008024:Ligands; D049268:Positron-Emission Tomography / Q000379:methods*; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013552:Swine
D003287:Contrast Media; D005462:Fluorine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals