N-[11C]methylspiperone PET, in contrast to [11C]raclopride, fails to detect D2 receptor occupancy by an atypical neuroleptic

被引:32
作者
Hagberg, G [1 ]
Gefvert, O
Bergström, M
Wieselgren, IM
Lindström, L
Wiesel, FA
Långström, B
机构
[1] Univ Uppsala Hosp, PET Ctr, S-75185 Uppsala, Sweden
[2] Uppsala Univ, Dept Psychiat Res, Vasteras Cent Hosp, S-72189 Vasteras, Sweden
[3] Univ Uppsala Hosp, Dept Psychiat, S-75017 Uppsala, Sweden
[4] Uppsala Univ, PET Ctr, Uppsala, Sweden
关键词
positron emission tomography; C-11]raclopride; N-[C-11]methylspiperone; quetiapine; schizophrenia; dopamine receptors;
D O I
10.1016/S0925-4927(98)00020-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The occupancy of the atypical neuroleptic quetiapine (Seroquel) at the D-2 dopamine receptor was investigated using the PET tracers [C-11]raclopride and N-[C-11]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 D-2, 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 [C-11]raclopride (P < 0.01), no such trend was apparent for N-[C-11]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-[C-11]methylspiperone cannot be used for the assessment of D-2, receptor occupancy induced by quetiapine. The result is discussed in terms of endogenous dopamine, tracer kinetics and equilibrium dissociation constants. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:147 / 160
页数:14
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