Dopamine D1 receptor imaging in the rodent and primate brain using the isoquinoline +-[11C]A-69024 and positron emission tomography.
In vivo pharmacokinetic and brain binding characteristics of (+)-[(11)C]A-69024, a high-affinity-D1-selective dopamine receptor antagonist, were assessed with micro-PET and beta-microprobes in the rat and PET in the baboon. The biodistribution of (+)-[(11)C]A-69024 in rats and baboons showed a rapid brain uptake (reaching a maximal value at 5 and 15 min postinjection in rats and baboons, respectively), followed by a slow wash out. The region/cerebellum concentration ratio was characterized by a fourfold higher uptake in striatum and a twofold higher uptake in cortical regions, consistent with in vivo specific binding of the radiotracer in these cerebral regions. Furthermore, this specific (+)-[(11)C]A-69024 binding significantly correlated with the reported in vitro distribution of dopamine D1-receptors. Finally, the specific uptake of the tracer in the striatum and cortical regions was completely prevented by either a pretreatment with large doses of nonradioactive (+/-)A-69024 or of the D1-selective antagonist SCH23390, resulting in a similar uptake in the reference region (cerebellum) and in other brain regions. Thus, (+)-[(11)C]A-69024 appears to be a specific and enantioselective radioligand to visualize and quantify brain dopamine D1 receptors in vivo using positron emission tomography.
Besret
Laurent
L
CNRS, URA 2210, 4 place du Général Leclerc, F-91406 Orsay, France.
Dollé
Frédéric
F
Hérard
Anne-Sophie
AS
Guillermier
Martine
M
Demphel
Stéphane
S
Hinnen
Françoise
F
Coulon
Christine
C
Ottaviani
Michèle
M
Bottlaender
Michel
M
Hantraye
Philippe
P
Kassiou
Michael
M
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D010208:Papaverine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D013045:Species Specificity; D044005:Tetrahydroisoquinolines / Q000493:pharmacokinetics