Analysis of neuroreceptor binding in the living brain for molecular imaging

Neuroreceptor imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) allows us to directly investigate the pathophysiology of neurological disease or drug-receptor interactions in the living human brain. Imaging technologies can identify molecular targets of new drugs and have become indispensable for drug discovery and development. In recent years, many neuroreceptor imaging studies in the living brain have been conducted using radiolabeled ligand. Unfortunately, our present knowledge of ligand-receptor interactions and metabolism in the living brain remains insufficient. Generally, in vivo receptor binding is considered to be affected by several factors such as local blood flow, endogenous ligands or internalization of receptors. However, in vivo receptor binding has the potential of also being altered by other microenvironmental factors surrounding the receptor. The living brain is a complex organ consisting of intercommunicating neurons and in vitro systems reflect only part of the complexity of living systems. Therefore, studies of the neural functions and dynamics of small molecular compounds in the living brain are an important for the understanding of biochemical abnormalities relating to disease. The study of neuroreceptor function in the living brain will be an essential and integral component of drug discovery and novel therapeutics. This review describes evidence that neuroreceptor binding or enzyme in the living brain may be affected by neuronal microenvironmental factors that do not occur in vitro. The utility of animal imaging using radiolabeled small molecular probes for drug discovery and development is discussed.