IN-VIVO IMAGING OF NEUROTRANSMITTER SYSTEMS USING RADIOLABELED RECEPTOR LIGANDS

In vivo functional brain imaging, including global blood flow, regiona l cerebral blood flow (rCBF), measured with positron emission tomograp hy (PET) and single photon emission computed tomography (SPECT), and r egional cerebral metabolic rate (rCMR) measured with deoxyglucose PET, have been widely used in studies of psychiatric disorders. These stud ies have found modest differences and required large numbers of patien ts. Activation studies using rCBF or rCMR as indices of neuronal activ ity are more sensitive because patients act as their own control; howe ver, findings localize regions of change but provide no data about spe cific neurotransmitter systems. After a general discussion of the role of neurotransmitter systems in neuropsychiatric disorders, an overvie w of the methodology of development and selection of radioligands for PET and SPECT is presented. Studies involving PET and SPECT ligand met hods are reviewed and their findings summarized, including recent work demonstrating successive mutual modulation of neurotransmitter system s. Kinetic and equilibrium analysis modeling are reviewed. the emergin g methodology of measuring neurotransmitter release on activation, bot h pharmacologically and by task performance, using ligand methods is r eviewed and proposed as a promising new approach for studying psychiat ric disorders. (C) American College of Neuropsychopharmacology. Publis hed by Elsevier Science Inc.