Molecular Imaging of Dopamine Partial Agonists in Humans: Implications for Clinical Practice

Area of Science:

• Neuroscience
• Psychopharmacology
• Radiopharmacology

Background:

• Positron emission tomography (PET) has been crucial since the late 1980s for assessing antipsychotic drug engagement with D2/3 receptors.
• Established guidelines suggest 65-80% D2/3 receptor occupancy for optimal efficacy and minimal side effects with typical antipsychotics.

Purpose of the Study:

• To review available PET studies on partial agonist antipsychotics (aripiprazole, brexpiprazole, cariprazine).
• To determine optimal target engagement levels for partial agonists and their relationship with clinical outcomes.
• To guide individualized patient treatment based on optimal plasma levels derived from PET data.

Main Methods:

• Review of existing Positron Emission Tomography (PET) studies.
• Analysis of D2/3 receptor occupancy data for partial agonist antipsychotics.
• Correlation of receptor occupancy with clinical effects and side effects.

Main Results:

• Partial agonist antipsychotics demonstrate a different occupancy-efficacy relationship compared to antagonists.
• High target engagement (>90%) is necessary for the antipsychotic efficacy of partial agonists.
• Optimal plasma levels for partial agonists can be determined from PET data.

Conclusions:

• Partial agonist antipsychotics, including aripiprazole, brexpiprazole, and cariprazine, require high D2/3 receptor occupancy (>90%) for optimal efficacy.
• PET imaging provides valuable data for optimizing treatment with these agents.
• Findings can inform clinical practice for personalized antipsychotic therapy.