Positron-emitting N-[18F]fluoroalkyl and [18F]fluoropyrrolidinyl analogues of eticlopride as potential in vivo radioligands for dopamine D2 receptors.
N-Fluoroalkyl and 4-fluoropyrrolidinyl eticlopride analogues with high affinity toward central nervous system dopamine D2 receptors in vitro were labelled with positron emitting fluorine-18 (t1/2 = 110 min), and their in vivo biodistribution was investigated in rats. N-[18F]Fluoro-ethyl and -propyl eticlopride derivatives showed poor in vivo selectivity in the rat brain. On the other hand, 4-[18F]fluoropyrrolidinyl eticlopride exhibited almost constant and relatively high striatal concentration. The striatal/cerebellar radioactivity ratio, which corresponds to the ratio of a brain D2 receptor-rich to poor region, gradually increased to 5.2-6.4, 90 min after the injection. The striatal accumulation was selectively inhibited by pre-injection of haloperidol, a dopamine D2 antagonist, without affecting accumulation in other tissues. Thus, the selective striatal accumulation of 4-[18F]fluoropyrrolidinyl eticlopride in striatal tissue appears to be due to the specific binding to dopamine D2 receptors.
Maeda
M
M
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Sasaki
S
S
Fukumura
T
T
Fukuzawa
E
E
Watanabe
K
K
Kojima
M
M
Tahara
T
T
Masuda
K
K
Ichiya
Y
Y
D000818:Animals; D004583:Electrons; D005462:Fluorine Radioisotopes; D008024:Ligands; D008297:Male; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012457:Salicylamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
D005462:Fluorine Radioisotopes; D008024:Ligands; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C074472:4-fluoroeticlopride; C045989:eticlopride