N-[11C]methylspiperone PET, in contrast to [11C]raclopride, fails to detect D2 receptor occupancy by an atypical neuroleptic.
The occupancy of the atypical neuroleptic quetiapine (Seroquel) at the D2 dopamine receptor was investigated using the PET tracers [11C]raclopride and N-[11C]methylspiperone in a group of five schizophrenic patients. A steady-state treatment condition was ensured by dosing the patients with 750 mg quetiapine daily during 3 weeks followed by a period of tapering off the dose. For each patient, PET examinations were performed with both tracers at two of the following doses: 750, 450, 300 and/or 150 mg. As control, a group of six healthy untreated volunteers was investigated. The D2 binding potential in the putamen and the caudate nucleus was determined by using an evaluation method based on the method proposed by Patlak and Blasberg. The receptor occupancy was determined by assuming that the group of healthy volunteers is representative of untreated drug-naive schizophrenic patients. While a significant linear trend of increasing occupancy with increasing quetiapine dose (reaching 51% +/- 10% occupancy at the 750 mg dose) was detected with [11C]raclopride (P < 0.01), no such trend was apparent for N-[11C]methylspiperone (P > 0.09, maximal occupancy values were 2% +/- 3%, measured for the group of three patients on 450 mg). The study suggests that N-[11C]methylspiperone cannot be used for the assessment of D2 receptor occupancy induced by quetiapine. The result is discussed in terms of endogenous dopamine, tracer kinetics and equilibrium dissociation constants.
Hagberg
G
G
Uppsala University PET Centre, University Hospital, Sweden. gisela.hagberg@pet.uu.se
Gefvert
O
O
Bergström
M
M
Wieselgren
I M
IM
Lindström
L
L
Wiesel
F A
FA
Långström
B
B
D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D003987:Dibenzothiazepines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011699:Putamen / Q000378:metabolism; D000069348:Quetiapine Fumarate; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides; D012559:Schizophrenia / Q000378:metabolism; D013134:Spiperone / Q000031:analogs & derivatives*; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D000069348:Quetiapine Fumarate; D020891:Raclopride; D013134:Spiperone; C039167:3-N-methylspiperone; D004298:Dopamine