Introduction

Since the development of neuroreceptor positron emission tomography (PET) imaging in the 1980s, the application of this novel in-vivo technology has revolutionized the study of schizophrenia for pathophysiology and drug development. This now-coined “molecular imaging” in schizophrenia has a historical root in the very basis of in-vivo neuroreceptor imaging with PET and single-photon emission computed tomography (SPECT). Indeed, the first successful imaging study in 1983 in living human brain was with a radiolabeled antipsychotic, spiperone (Spiroperidol), labeled with [11C]-methyl iodine (Wagner et al.,1983), and later with [18F]. This was followed with the isotopic labeling of [11C]-raclopride (i.e. no change in the chemical structure or pharmacology), also an antipsychotic and D2/D3 dopamine (DA) antagonist. Both unlabeled spiperone and raclopride have been studied for their potential therapeutic value for schizophrenia in clinical trials. Although neither of these antipsychotics was used clinically, their radiolabeled PET analogs led the way for studying D2-like dopamine receptors, and opened up the entire field of studying neuroreceptors as essentially a new subspecialty of neuroimaging with tremendous application in neuropsychiatry. These two radiotracers were quickly shown to be displaceable by unlabeled marketed antipsychotics such as haloperidol (Haldol), which led ultimately to dopamine D2/D3 occupancy studies (see below), and guidance of therapeutic drug dose levels now being visualized in human brain. Most importantly, they illustrate the merging of basic psychopharmacology, CNS nuclear medicine methodology, and in-vivo neuropsychiatric applications.