Imaging Synaptic Density in the Human Brain with PET

A wide variety of neuropsychiatric diseases involve the loss of neurons and synapses. Recently, we developed a new PET radiopharmaceutical, [C-11]UCB-J, which binds selectively to a synaptic vesicle protein, SV2A. This target is ubiquitously expressed in the brain, and thus provides an imaging paradigm to measure synaptic density in humans. The presentation will include the development of this ligand, the in vivo and ex vivo validation studies in nonhuman primates, healthy human studies including test/retest scans, kinetic modeling, and blocking studies to identify reference regions. Initial patient results are shown in temporal lobe epilepsy, where UCB-J shows much larger ipsilateral/contralateral asymmetries than FDG, and in Alzheimer’s disease, which showed a large (~40%) reduction in hippocampus and entorhinal cortex.