Narendran R, Jedema H P, Lopresti B J, Mason N S, Gurnsey K, Ruszkiewicz J, Chen C-M, Deuitch L, Frankle W G, Bradberry C W
1] Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA [2] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Mol Psychiatry. 2014 Mar;19(3):302-10. doi: 10.1038/mp.2013.9. Epub 2013 Feb 26.
In a recent human positron emission tomography (PET) study we demonstrated the ability to detect amphetamine-induced dopamine (DA) release in the prefrontal cortex as a reduction in the binding of the DA D(2/3) radioligand [(11)C]FLB 457. A key requirement for validating this paradigm for use in clinical studies is demonstrating that the changes in [(11)C]FLB 457 binding observed with PET following amphetamine are related to changes in dialysate DA concentration as measured with microdialysis. Microdialysis and PET experiments were performed to compare, in five rhesus monkeys, amphetamine-induced DA release and [(11)C]FLB 457 displacement in the frontal cortex after three doses of amphetamine (0.3 mg kg(-1), 0.5 mg kg(-1) and 1.0 mg kg(-1)). Amphetamine led to a significant dose-dependent increase in dialysate (0.3 mg kg(-1): 999±287%; 0.5 mg kg(-1): 1320±432%; 1.0 mg kg(-1): 2355±1026%) as measured with microdialysis and decrease in [(11)C]FLB 457 binding potential (BP(ND), 0.3 mg kg(-1): -6±6%; 0.5 mg kg(-1): -16±4%; 1.0 mg kg(-1): -24±2%) as measured with PET. The relationship between amphetamine-induced peak ΔDA and Δ[(11)C]FLB 457 BP(ND) in the frontal cortex was linear. The results of this study clearly demonstrate that the magnitude of dialysate DA release is correlated with the magnitude of the reduction in [(11)C]FLB 457 BP(ND) in the frontal cortex. The use of the [(11)C]FLB 457-amphetamine imaging paradigm in humans should allow for characterization of prefrontal cortical DA release in neuropsychiatric disorders such as schizophrenia and addiction.
在最近一项人体正电子发射断层扫描（PET）研究中，我们证明了能够检测到苯丙胺引起的前额叶皮质多巴胺（DA）释放，表现为DA D(2/3)放射性配体[(11)C]FLB 457结合的减少。验证此范式用于临床研究的一个关键要求是证明PET观察到的苯丙胺给药后[(11)C]FLB 457结合变化与微透析测量的透析液DA浓度变化相关。进行了微透析和PET实验，以比较五只恒河猴在给予三剂苯丙胺（0.3 mg kg(-1)、0.5 mg kg(-1)和1.0 mg kg(-1)）后，前额叶皮质中苯丙胺诱导的DA释放和[(11)C]FLB 457置换情况。苯丙胺导致微透析测量的透析液显著剂量依赖性增加（0.3 mg kg(-1)：999±287%；0.5 mg kg(-1)：1320±432%；1.0 mg kg(-1)：2355±1026%），以及PET测量的[(11)C]FLB 457结合势（BP(ND)）降低（0.3 mg kg(-1)：-6±6%；0.5 mg kg(-1)：-16±4%；1.0 mg kg(-1)：-24±2%）。前额叶皮质中苯丙胺诱导的峰值ΔDA与Δ[(11)C]FLB 457 BP(ND)之间的关系呈线性。本研究结果清楚地表明，透析液DA释放的幅度与前额叶皮质中[(11)C]FLB 457 BP(ND)降低的幅度相关。在人类中使用[(11)C]FLB 457-苯丙胺成像范式应有助于在精神分裂症和成瘾等神经精神疾病中表征前额叶皮质DA释放情况。
