Dopamine D receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia.

Dopamine D receptor occupancy (DRO) is a key feature of all currently approved antipsychotic medications. However, antipsychotic efficacy associated with high DRO is often limited by side effects such as motor disturbances and hyperprolactinemia. Lumateperone (ITI-007) is a first-in-class selective and simultaneous modulator of serotonin, dopamine and glutamate in development for the treatment of schizophrenia and other disorders.

Evaluation of F-RO-948 PET for Quantitative Assessment of Tau Accumulation in the Human Brain.

The availability of tau PET radioligands enables quantitative assessment of tau density and distribution in the human brain. We evaluated the kinetics of a novel radioligand, F-RO-948 (previously referred to as F-RO6958948), and its ability to identify tau positivity in individual patients with mild Alzheimer disease (AD). Eleven subjects with amyloid-positive mild AD, 5 amyloid-negative older control subjects (OC), and 5 younger control subjects (YC) completed 1 or 2 (4 AD and 5 OC) PET scans with F-RO-948 for 90, 120, or 200 min.

Characterization of 3 Novel Tau Radiopharmaceuticals, C-RO-963, C-RO-643, and F-RO-948, in Healthy Controls and in Alzheimer Subjects.

C-RO-963, C-RO-643, and F-RO-948 (previously referred to as C-RO6924963, C-RO6931643, and F-RO6958948, respectively) have been reported as promising PET tracers for tau imaging based on in vitro and preclinical PET data. Here we describe the first, to our knowledge, human evaluation of these novel radiotracers. Amyloid PET-positive Alzheimer disease (AD) subjects and younger controls each received 2 different tau tracers.

Brain PET Imaging of α7-nAChR with [18F]ASEM: Reproducibility, Occupancy, Receptor Density, and Changes in Schizophrenia.

Background: The α7 nicotinic acetylcholine receptor increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7 nicotinic acetylcholine receptor suggests a role in cognition.

Methods: We expanded the first-in-human PET imaging of α7 nicotinic acetylcholine receptor with [18F]ASEM from 5 to 21 healthy nonsmoking volunteers and added a feasibility study in 6 male patients with schizophrenia.

ITI-007 demonstrates brain occupancy at serotonin 5-HT₂A and dopamine D₂ receptors and serotonin transporters using positron emission tomography in healthy volunteers.

Rationale: Central modulation of serotonin and dopamine underlies efficacy for a variety of psychiatric therapeutics. ITI-007 is an investigational new drug in development for treatment of schizophrenia, mood disorders, and other neuropsychiatric disorders.

Objectives: The purpose of this study was to determine brain occupancy of ITI-007 at serotonin 5-HT2A receptors, dopamine D2 receptors, and serotonin transporters using positron emission tomography (PET) in 16 healthy volunteers.

Human brain imaging of α7 nAChR with [(18)F]ASEM: a new PET radiotracer for neuropsychiatry and determination of drug occupancy.

Purpose: Using the α7-nAChR radiotracer, [(18)F]ASEM, we present the first successful human positron emission tomography (PET) studies. Rodent occupancy with three clinically employed α7-nAChR drugs confirms the specificity of the radiotracer.

Procedures: Five healthy male subjects were imaged for 90 min following IV [(18)F]ASEM.