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

Area of Science:

• Neuroscience
• Pharmacology
• Radiochemistry

Background:

• Positron emission tomography (PET) with the dopamine D(2/3) radioligand [(11)C]FLB 457 can detect amphetamine-induced dopamine (DA) release in the human prefrontal cortex.
• Validating this imaging paradigm for clinical use requires correlating PET findings with direct measures of DA release.

Purpose of the Study:

• To validate the [(11)C]FLB 457 PET imaging paradigm by comparing amphetamine-induced DA release measured with microdialysis to changes in [(11)C]FLB 457 binding in non-human primates.
• To establish the relationship between DA concentration and radioligand binding reduction following amphetamine administration.

Main Methods:

• PET imaging and microdialysis were conducted in five rhesus monkeys.
• Animals received three doses of amphetamine (0.3, 0.5, and 1.0 mg/kg).
• Dialysate DA concentration and [(11)C]FLB 457 binding potential (BP(ND)) in the frontal cortex were measured.

Main Results:

• Amphetamine caused a dose-dependent increase in dialysate DA release (up to 2355±1026%).
• A corresponding dose-dependent decrease in [(11)C]FLB 457 BP(ND) was observed with PET (up to -24±2%).
• A linear correlation was found between peak DA release and the reduction in [(11)C]FLB 457 BP(ND).

Conclusions:

• The [(11)C]FLB 457-amphetamine PET imaging paradigm accurately reflects amphetamine-induced dopamine release in the frontal cortex.
• This validated method can be used to characterize prefrontal cortical DA release in neuropsychiatric disorders like schizophrenia and addiction.