Striatal and extrastriatal dopamine D2 receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: a positron emission tomography study with [11C]raclopride and [11C]FLB457

Rationale Second-generation antipsychotics demonstrateclinical efficacy with fewer extrapyramidal side effects comparedwith first-generation antipsychotics. One of the proposedexplanations is the hypothesis of preferentialextrastriatal dopamine D2 receptor occupancy (limbic selectivity)by antipsychotics. In the present study, we focused onaripiprazole, which has a unique pharmacological profile withpartial agonismat dopamineD2 receptors and the minimal riskof extrapyramidal side effects. Previous positron emissiontomography (PET) studies using high-affinity radioligandsfor dopamine D2 receptors have reported inconsistent resultsregarding regional differences of dopamine D2 receptor occupancyby aripiprazole

Imaging of Tau and Amyloid Pathology in Patients with Traumatic Brain Injury: A PET Study Usinig [11C]PBB3 and [11C]PIB

Backgrounds: Chronic traumatic encephalopathy (CTE) is a delayed-onset neurodegenerative disease, which occurs several years after traumatic brain injury (TBI). Pathologically, CTE is characterized by abnormal accumulations including tau changes, amyloid-beta proteins. Using a novel tau ligand [11C]PBB3 and amyloid ligand [11C]PIB, we explored in vivo imaging of tau and amyloid pathology in TBI patients.Methods: Three patients with repetitive mild TBI (2 wrestlers, 1 kick boxer), two patients with single severe TBI (1 diffuse axonal injury, 1 acute subdural hematoma) and 20 age-matched healthy controls (HCs) underwent MRI and PET scans using [11C]PBB3 and [11C]PIB. For each PET data, standardized uptake value ratio (SUVR) using cerebellum as a reference region was calculated. Amyloid deposition was evaluated by visual assessment of SUVR images of [11C]PIB PET. Tau deposition was evaluated by visual assessment and VOI analysis of SUVR images of [11C]PBB3 PET. Cognitive impairments were also evaluated with neuropsychological tests.Results: In HCs, none was [11C]PBB3- or [11C]PIB-positive. In TBI patients, memory impairment was the most frequent symptom. All TBI patients were [11C]PIB-negative, indicating absence of amyloid beta deposition. In contrast, four of five TBI patients showed high [11C]PBB3 binding in the medial temporal cortex. High [11C]PBB3 binding was also observed in the insular and the frontal cortex. Some of these [11C]PBB3-binding regions exhibited local cortical atrophy. Cortical atrophy was present in some of these regions.Conclusions: These preliminary findings provided the evidence of TBI-induced tau pathology consistent with postmortem studies.Annual Meeting of Society of Biological Psychiatr