Imaging in Central Nervous System Drug Discovery

Area of Science:

• Neuroscience
• Pharmacology
• Medical Imaging

Background:

• Central nervous system (CNS) drug discovery is resource-intensive and high-risk.
• High failure rates necessitate efficient decision-making processes.
• PET imaging has become integral to CNS drug development over the past two decades.

Purpose of the Study:

• To review the role of PET imaging in CNS drug development.
• To discuss how PET evaluates the "3 pillars" of drug survival: tissue exposure, target engagement, and pharmacologic activity.
• To highlight advances in PET science enabling sophisticated human studies.

Main Methods:

• Review of current literature on PET imaging in CNS drug development.
• Analysis of PET's application in assessing key drug survival metrics.
• Examination of advancements in PET biomarker development and analytical techniques.

Main Results:

• PET imaging provides critical decision-making tools in early-phase CNS drug studies.
• Evaluation of the "3 pillars" using PET enhances confidence in progressing drug candidates.
• PET facilitates early identification of non-viable compounds, saving resources.
• Advances in PET science support complex drug development studies in humans.

Conclusions:

• PET imaging significantly de-risks CNS drug development by providing objective data on drug efficacy and safety.
• The "3 pillars" framework, assessed by PET, is vital for optimizing drug candidate selection and progression.
• Ongoing advancements in PET technology and biomarkers will further enhance its utility in CNS drug discovery and development.