Positron emission tomography and its use to image the occupancy of drug binding sites

The development of positron emission tomography (PET) and the ability to synthesize compounds labeled with the short-lived positron emitters C-11 and F-18 has made possible the imaging and quantification of drug binding sites in the human body. By conducting PET studies with an appropriate radioligand before and after treatment with a drug, the fraction of the total number of binding sites that is occupied by the drug (the "occupancy" of the site) can often be determined. To the extent that occupancy is a good indicator of pharmacological activity, such PET experiments can aid the development of drug dosage regimens. Some of the general issues involved in PET studies of drug occupancy are discussed. There have been many such studies involving antipsychotic drugs and dopamine D-2 receptor radioligands. Since neuroleptics have been extensively reviewed elsewhere, only the major findings are discussed here. Other binding sites (and drug classes) in the dopamine system to which this methodology has been applied include: the dopamine transporter (stimulant drugs) and monoamine oxidase A and B (antidepressant drugs). Occupancy studies are also possible for many drug targets beyond the dopamine system. (C) 2003 Wiley-Liss, Inc.