Hagberg G, Gefvert O, Bergström M, Wieselgren I M, Lindström L, Wiesel F A, Långström B
Uppsala University PET Centre, University Hospital, Sweden.
Psychiatry Res. 1998 Jun 30;82(3):147-60. doi: 10.1016/s0925-4927(98)00020-1.
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.
在一组5名精神分裂症患者中，使用PET示踪剂[11C]雷氯必利和N-[11C]甲基哌啶酮研究了非典型抗精神病药物喹硫平（思瑞康）对D2多巴胺受体的占有率。通过在3周内每天给患者服用750 mg喹硫平，随后逐渐减少剂量，确保达到稳态治疗条件。对于每位患者，在以下剂量中的两个剂量下使用两种示踪剂进行PET检查：750、450、300和/或150 mg。作为对照，对一组6名未接受治疗的健康志愿者进行了研究。使用基于Patlak和Blasberg提出的方法的评估方法，测定壳核和尾状核中的D2结合潜力。通过假设健康志愿者组代表未接受治疗的未用过药的精神分裂症患者来确定受体占有率。使用[11C]雷氯必利检测到随着喹硫平剂量增加占有率呈显著线性趋势增加（在750 mg剂量时达到51%±10%占有率）（P<[11C]雷氯必利检测到随着喹硫平剂量增加占有率呈显著线性趋势增加（在750 mg剂量时达到51%±10%占有率）（P<0.01），而对于N-[11C]甲基哌啶酮则没有这种趋势（P>0.09，在450 mg剂量的三名患者组中测得的最大占有率值为2%±3%）。该研究表明，N-[11C]甲基哌啶酮不能用于评估喹硫平诱导的D2受体占有率。根据内源性多巴胺、示踪剂动力学和平衡解离常数对结果进行了讨论。 0.01），而对于N-[11C]甲基哌啶酮则没有这种趋势（P>0.09，在450 mg剂量的三名患者组中测得的最大占有率值为2%±3%）。该研究表明，N-[11C]甲基哌啶酮不能用于评估喹硫平诱导的D2受体占有率。根据内源性多巴胺、示踪剂动力学和平衡解离常数对结果进行了讨论。
