Gjedde A, Wong D F
Department of Neurology and Neurosurgery, Montreal Neurological Institute, Canada.
Neurosurg Rev. 1987;10(1):9-18. doi: 10.1007/BF01780587.
The radioligand 3-N-[11C]methylspiperone (11C-NMSP) binds to D2 dopamine receptors with high affinity. We determined the rate of binding in 12 male volunteers, using a 3-compartment model to relate the time integral of the tracer plasma concentration to the distribution of the tracer in the caudate nucleus measured by positron tomography. The rate of binding (k3) was defined as the product of the bimolecular association rate (kon) and the quantity of available receptors (B'max). We calculated the product as the ratio between the steady-state rate of accumulation and the volume of distribution in the caudate nucleus. The average value was 0.100 min-1 in the normal volunteers. We varied k3 by reducing the number of available receptors with the D2 dopamine receptor blocking agent haloperidol ingested 4 hours before the tracer injection. In the normal volunteers, we calculated a receptor density of 17 pmol g-1 in the caudate nucleus and an inhibitory constant of haloperidol of 3 nM by comparing tracer accumulation in the absence and presence of the blocking agent. Bmax was also calculated in older men, drug-naive schizophrenics, and drug-treated schizophrenics (all men). The lowest value of Bmax was calculated in the older men (6 pmol g-1); the highest in the two groups of schizophrenic patients (39 and 41 pmol g-1, respectively).
放射性配体3-N-[11C]甲基螺哌隆（11C-NMSP）与D2多巴胺受体具有高亲和力。我们使用三室模型确定了12名男性志愿者的结合率，该模型将示踪剂血浆浓度的时间积分与通过正电子断层扫描测量的示踪剂在尾状核中的分布相关联。结合率（k3）被定义为双分子缔合率（kon）与可用受体数量（B'max）的乘积。我们将该乘积计算为稳态积累率与尾状核分布体积之间的比率。正常志愿者的平均值为0.100 min-1。在注射示踪剂前4小时摄入D2多巴胺受体阻断剂氟哌啶醇，通过减少可用受体数量来改变k3。在正常志愿者中，通过比较有无阻断剂时的示踪剂积累情况，我们计算出尾状核中的受体密度为17 pmol g-1，氟哌啶醇的抑制常数为3 nM。还计算了老年男性、未服用过药物的精神分裂症患者和接受药物治疗的精神分裂症患者（均为男性）的Bmax。Bmax的最低值在老年男性中计算得出（6 pmol g-1）；在两组精神分裂症患者中最高（分别为39和41 pmol g-1）。
