Development of 18F-labeled agonist radioligands for PET imaging of the high-affinity state of cerebral dopamine D2/3 receptors

Positron emission tomography (PET) is a powerful technique for medical imaging. It allows visualizing and quantitatively describing physiological processes in the living body with the aid of radioactively labeled compounds called tracers.
Dopamine is an important neurotransmitter - a compound that brain neurons need in order to communicate with each other. Such communication (signaling) takes place when dopamine is released from one neuron and binds to the receptors on the other neuron.
In many neuropsychiatric disorders such as Parkinson's disease, schizophrenia and substance abuse, the number and functioning of dopamine receptors is thought to be different from the healthy state. Imaging of dopamine receptors by PET can therefore be used to diagnose neuropsychiatric disorders and/or to understand how they develop. Dopamine receptors belonging to the second and third (D2/3) subtypes are most often imaged by PET.
Receptors of each subtype can exist two interconvertible states with high and low affinity for dopamine. One hypothesis suggests that the high-affinity state is the “functional” subset of all receptors, which is primarily responsible for the signaling. Imaging only the high-affinity state should then provide more valuable information about the state of the brain than imaging both affinity states together. However, most existing PET tracers for dopamine receptors do not distinguish between affinity states.
In this research project we attempted to develop new PET tracers that would preferentially recognize the high-affinity state of dopamine D2/3 receptors and be suitable for widespread clinical use.