Role of human and animal PET studies in drug development

Positron emission tomography (PET) is the most selective and sensitive method for measuring molecular pathways and interactions in vivo. Within the area of drug development, PET can be used in several ways. The drug itself can be labelled with a positron emitter. This enables direct PET measurements of tissue drug concentrations, allowing for an assessment as to whether these concentrations are high enough for therapeutic purposes. A second application is the measurement of perfusion or metabolism during or following treatment. The best known example is the measurement of tumour metabolism as a marker of response to chemotherapy. Finally, mechanisms of action can be measured directly. In particular, receptor occupancy or enzyme inhibition can be measured using established radioligands for the molecular targets under investigation. Occupancy can be measured as a function of both administered dose and time after drug administration, allowing for optimal dose and dosing regimens to be determined based on only a small number of subjects. PET studies in experimental animals open up further possibilities. By using appropriate models of disease, effects due to progression of disease and those due to acute or chronic therapy can be studied separately even in the same animal.