Imaging dopamine transmission in the frontal cortex: a simultaneous microdiaysis and [11C]FLB 457 PET study

• Published in: Molecular psychiatry Vol. 19; no. 3; pp. 302 - 310
• Main Authors: Narendran, Rajesh, Jedema, Hank P., Lopresti, Brian J., Mason, Neale Scott, Gurnsey, Kate, Ruszkiewicz, James, Chen, Chi-Min, Deuitch, Lora, Frankle, W. Gordon, Bradberry, Charles W.
• Format: Journal Article
• Language: English
• Published: 26.02.2013
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2013.9

In a recent human PET study we demonstrated the ability to detect amphetamine-induced dopamine release in the prefrontal cortex as a reduction in the binding of the dopamine 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 dopamine concentration as measured with microdialysis. Microdialysis and PET experiments were performed to compare, in five rhesus monkeys, amphetamine-induced dopamine release and [ 11 C]FLB 457 displacement in the frontal cortex after three doses of amphetamine (0.3 mg/kg, 0.5 mg/kg, and 1 mg/kg). Amphetamine led to a significant dose-dependent increase in dialysate dopamine (DA, 0.3 mg/kg: 999 ± 287%; 0.5 mg/kg: 1320 ± 432%; 1.0 mg/kg: 2355 ± 1026%) as measured with microdiaysis and decrease in [ 11 C]FLB 457 binding potential (BP ND, 0.3 mg/kg: −6 ± 6%; 0.5 mg/kg: −16 ± 4%; 1.0 mg/kg: −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 dopamine 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 dopamine release in neuropsychiatric disorders such as schizophrenia and addiction.