PET in neurotherapeutic discovery and development

Area of Science:

• Neuroscience
• Radiochemistry
• Pharmacology

Background:

• Positron emission tomography (PET) is a sensitive, quantitative imaging technique.
• PET allows in vivo tracking of radiolabeled molecules without altering their properties.
• It is a valuable tool in drug discovery from preclinical to clinical stages.

Purpose of the Study:

• To discuss the application of PET radioligands in central nervous system (CNS) drug discovery and development.
• To highlight recent advances in psychiatry, neuro-oncology, and neurodegeneration.
• To explore challenges in developing novel CNS radiotracers.

Main Methods:

• Utilizing positron-emitting radionuclides incorporated into molecules of interest.
• Assessing pharmacokinetic and pharmacodynamic (PK/PD) characteristics in vivo.
• Developing and applying novel radiotracers for specific CNS targets.

Main Results:

• PET facilitates biomarker validation, PK/PD assessment, and target engagement studies.
• Applications include 5-HT2A, 11β-HSD1, KRASG12C, ATM, ALK2, amyloid beta plaques, and MAPK p38.
• PET aids in determining optimal dosing regimens and patient selection for clinical trials.

Conclusions:

• PET imaging is crucial for advancing CNS drug discovery and development.
• It provides quantitative insights into biomarker function and therapeutic response.
• Novel PET radioligands offer significant potential for understanding and treating neurological disorders.