In vivo imaging of neuromodulatory synaptic transmission using PET: A review of relevant neurophysiology

Recent data from positron emission tomography (PET) imaging studies suggest the possibility of studying synaptic transmission in vivo in humans. The approach will require a synthesis of two established techniques: brain activation studies (conventionally performed by measuring regional cerebral blood flow or metabolism) and neurotransmitter receptor imaging (using radiolabelled ligands that bind to specific neuroreceptors). By comparing neuroreceptor binding in subjects at rest and while performing an activation task, it may be possible to determine whether a particular neurotransmitter is involved in performance of the task. The underlying principle is that endogenous neurotransmitter competes with the injected radioligand for the same receptors, thereby inhibiting ligand binding. This effect will be even more pronounced during activation, as the synaptic concentration of transmitter rises. Thus, activation of a specific neurotransmitter will be detected as a decrease in specific binding of the radioligand. In this paper we review neurophysiological and biochemical literature to estimate the endogenous neurotransmitter concentration changes that will be expected to occur during an activation task, using the dopamine system as an example. We calculate that the average synaptic dopamine concentration is ≈ 100 nM and that it approximately doubles during activation. This, along with consideration of the concentration of radioligand and affinities of the ligand and dopamine for dopamine receptors, suggests that physiological activation of a specific neurotransmitter system is likely to be detectable with PET. © 1995 Wiley‐Liss, Inc.