Pharmacokinetic considerations in the PET and SPECT evaluation of CNS receptors

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are the only functional imaging methodologies that allow to evaluate, in vivo in human, specific binding proteins such as receptors, transporters or enzymes. PET and SPECT have already proved to be unique tools to follow, in the living human brain, the kinetics of the interaction of a radiolabelled ligand with its receptors. However, these imaging techniques measure the radioligand concentration in regions of interest (ROIs) as a function of time but they do not allow the direct measurement of the binding parameters, i.e. receptor concentration and radioligand affinity. To estimate these physiological parameters a mathematical model must be designed to simulate the kinetics of the radioligand. The modelling of the data obtained using such equilibrium or dynamic models allow to extract from the kinetic data these physiological parameters. PET and SPECT imaging methodologies have then opened a new era in brain biochemistry and have already important applicants in brain physiopathology, clinical pharmacology and drug development.