In molecular imaging of the brain, many factors affect the reliability of the quantitative information that can be derived from the imaging process. This article discusses factors impacting on the imaging quality that are related to the radiotracer per se. Following a brief summary of key concepts in receptor quantification, a number of these factors are discussed, including selectivity, affinity, delivery, and lipophilicity. Concepts discussed in the theoretical section are then illustrated, by reviewing a recent comparative evaluation of four agents developed to label the serotonin transporter ([(11)C]ADAM, [(11)C]DASB, [(11)C]DAPA, and [(11)C]AFM). Specifically, the relationship between affinity and lipophilicity, measured in vitro, and several scanning parameters are investigated. These include peripherical metabolism, brain uptake, required scanning time, nonspecific binding, and binding potential. It is shown that, within a given structural family, affinity and lipophilicity are associated with scan outcome in a relatively predictable manner.