Montgomery Andrew J, Asselin Marie-Claude, Farde Lars, Grasby Paul M
MRC Clinical Sciences Centre, Cyclotron Building, Imperial College, Hammersmith Hospital, London, UK.
J Cereb Blood Flow Metab. 2007 Feb;27(2):369-77. doi: 10.1038/sj.jcbfm.9600339. Epub 2006 May 10.
[(11)C]FLB 457 is a very high-affinity radiotracer that allows the measurement of dopamine D(2/3) receptor availability in regions of the brain where densities are very low, such as the cerebral cortex. It is not known if [(11)C]FLB 457 binding is sensitive to the concentration of endogenous dopamine in humans in a manner analogous to [(11)C]raclopride and [(123)I]IBZM in the striatum. To test this possibility, extrastriatal [(11)C]FLB 457 binding was measured at baseline and after the oral administration of 40 to 60 mg of the psychostimulant methylphenidate (MP) in 12 healthy volunteers using positron emission tomography (PET) in a balanced-order, double-blind design. The dynamic PET data were quantified using a two-tissue compartment model with a metabolite-corrected arterial plasma input function. Two volunteers were excluded because of excessive head movement. In the remainder, MP caused significant reductions in the volume of distribution (VD) in temporal and frontal cortical regions and thalamus, suggesting that [(11)C]FLB 457 binding is sensitive to endogenous dopamine concentration. Moreover, the change in [(11)C]FLB 457 binding after MP correlated with the dose of MP (in mg/kg body weight) in all regions assessed. We conclude that MP in doses within the therapeutic range for the treatment of attention deficit hyperactivity disorder causes increases in dopamine concentrations in extrastriatal regions and that [(11)C]FLB 457 PET may be a useful tool for the assessment of change in dopamine concentration in these areas in humans.
[(11)C]FLB 457是一种高亲和力放射性示踪剂，可用于测量大脑中密度极低区域（如大脑皮层）的多巴胺D(2/3)受体可用性。目前尚不清楚[(11)C]FLB 457结合是否像纹状体中的[(11)C]雷氯必利和[(123)I]IBZM那样，对人体内源性多巴胺浓度敏感。为了验证这种可能性，采用正电子发射断层扫描（PET）的平衡顺序双盲设计，对12名健康志愿者在基线状态下以及口服40至60毫克精神兴奋剂哌甲酯（MP）后，测量其纹状体以外区域的[(11)C]FLB 457结合情况。使用具有代谢物校正动脉血浆输入函数的双组织室模型对动态PET数据进行定量分析。两名志愿者因头部运动过度被排除。在其余志愿者中，MP导致颞叶、额叶皮质区域和丘脑的分布容积（VD）显著降低，这表明[(11)C]FLB 457结合对内源性多巴胺浓度敏感。此外，在所有评估区域中，MP给药后[(11)C]FLB 457结合的变化与MP剂量（以毫克/千克体重计）相关。我们得出结论，治疗注意力缺陷多动障碍的治疗范围内剂量的MP会导致纹状体以外区域多巴胺浓度升高，并且[(11)C]FLB 457 PET可能是评估人类这些区域多巴胺浓度变化的有用工具。
