title: Imaging dopamine transmission in the frontal cortex: a simultaneous microdialysis and [11C]FLB 457 PET study.
abstract: 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.
authors: 1] Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA [2] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors: R
authors: R
authors: Narendran
authors: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors: H P
authors: HP
authors: Jedema
authors: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors: B J
authors: BJ
authors: Lopresti
authors: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors: N S
authors: NS
authors: Mason
authors: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors: K
authors: K
authors: Gurnsey
authors: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors: J
authors: J
authors: Ruszkiewicz
authors: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors: C-M
authors: CM
authors: Chen
authors: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors: L
authors: L
authors: Deuitch
authors: 1] Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA [2] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors: W G
authors: WG
authors: Frankle
authors: 1] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA [2] VA Pittsburgh Health Services, Pittsburgh, PA, USA.
authors: C W
authors: CW
authors: Bradberry
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D059907:Functional Neuroimaging; D008253:Macaca mulatta; D008297:Male; D017551:Microdialysis; D049268:Positron-Emission Tomography; D011759:Pyrrolidines; D020891:Raclopride; D011869:Radioligand Assay; D012457:Salicylamides; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D012457:Salicylamides; C065065:FLB 457; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine