The use of PET imaging to detect and quantify receptor occupancy (RO) has become a translational standard in CNS discovery and clinical trials. For example, 18F radiolabeling of targeted small molecules enables a PET tracer-based PD biomarker. The tracer can be used for dynamic, non-invasive quantification of percentage RO.
For relevant targets, rodent models can be used to quickly and efficiently:
- Screen for specificity
- Validate the target using a cold blocking compound
- Generate a full dose-RO curve
- Compare candidate molecules
- Promising molecules can then be more confidently selected for NHP and/or first in human studies. This inherently also allows quantification of RO, and correlation with efficacy in future translational work.