Vulnerability of positron emission tomography radiotracers to endogenous competition. New insights.

PET and SPECT neuroreceptor imaging techniques combined with pharmacological challenges have been introduced to measure acute fluctuations of synaptic dopamine (DA) concentrations in the living human brain. Changes in the in vivo binding of radioligands following manipulation of transmitter levels are generally believed to be driven by binding competition between the radioligand and neurotransmitter. This imaging modalityhas been very successful in the study of DA transmission at D2 receptors. Yet, the extension of this technique to the study of other neurotransmitter systems has proven difficult. This paper reviews recent evidencesuggesting that simple binding competition might not be the only phenomenon regulating transmitter-radioligand interactions in vivo, and examines emerging data indicating that receptor trafficking might also be involved. A better understanding of the mechanisms underlying these interactions should facilitate the development of PET and SPECT radiotracers suitable for the reporting of synaptic transmitter levels.