Impact of bimekizumab and certolizumab pegol on efficacy, safety and osteoblastic activity in radiographic axial spondyloarthritis: results from a phase IIa, multicentre, randomised, double-blind, exploratory study with PET-CT imaging.

Background: The efficacy and safety of bimekizumab (BKZ), an inhibitor of interleukin (IL)-17F in addition to IL-17A, has been established in axial spondyloarthritis (axSpA). Early assessment of new bone formation is possible using F-fluoride positron emission tomography-computerised tomography (PET-CT) imaging to quantitatively monitor osteoblastic activity.

Objectives: This exploratory study, initiated before phase IIb/III studies, assessed the efficacy and safety of BKZ in patients with radiographic (r-)axSpA and its effect on new bone formation.

Evaluation and Application of a PET Tracer in Preclinical and Phase 1 Studies to Determine the Brain Biodistribution of Minzasolmin (UCB0599).

Purpose: Minzasolmin (UCB0599) is an orally administered, small molecule inhibitor of ASYN misfolding in development as a potential disease-modifying therapy for Parkinson's disease. Here we describe the preclinical development of a radiolabeled tracer and results from a phase 1 study using the tracer to investigate the brain distribution of minzasolmin.

Procedures: In the preclinical study, two radiolabeling positions were investigated on the S-enantiomer of minzasolmin (UCB2713): [C]methylamine UCB2713 ([C-N-CH]UCB2713) and [C]carbonyl UCB2713 ([C-CO]UCB2713).

Drug characteristics derived from kinetic modeling: combined C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A.

Background: Antiepileptic drugs, levetiracetam (LEV) and brivaracetam (BRV), bind to synaptic vesicle glycoprotein 2A (SV2A). In their anti-seizure activity, speed of brain entry may be an important factor. BRV showed faster entry into the human and non-human primate brain, based on more rapid displacement of SV2A tracer C-UCB-J.

Validation of Parametric Methods for [C]UCB-J PET Imaging Using Subcortical White Matter as Reference Tissue.

Purpose: The aim of this study was to evaluate different non-invasive methods for generating (R)-1-((3-([C]methyl)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) ([C]UCB-J) parametric maps using white matter (centrum semi-ovale-SO) as reference tissue.

Procedures: Ten healthy volunteers (8 M/2F; age 27.6 ± 10.

Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study.

The objective of this study was to assess the effect of secukinumab, a monoclonal antibody that inhibits interleukin (IL)-17A, on number of new active brain magnetic resonance imaging (MRI) lesions in subjects with relapsing-remitting multiple sclerosis (MS). Subjects (N = 73) were randomized 1:1 to secukinumab 10 mg/kg or placebo by intravenous infusion at weeks 0, 2, 4, 8, 12, 16, and 20. MRI scans were obtained within 30 days prior to randomization, on a monthly basis during the treatment period, and at study completion.

Decrease of mGluR5 receptor density goes parallel with changes in enkephalin and substance P immunoreactivity in Huntington's disease: a preliminary investigation in the postmortem human brain.

Group 1 metabotropic glutamate subtype 5 receptors (mGluR5) contribute to the control of motor behavior by regulating the balance between excitation and inhibition of outputs in the basal ganglia. The density of these receptors is increased in patients with Parkinson's disease and motor complications. We hypothesized that similar changes may occur in Huntington's disease (HD) and aimed at testing this hypothesis in a preliminary experimental series in postmortem human brain material obtained from HD patients.

Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[(18)F]FMeNER-D (2).

Purpose: In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner.

Consensus nomenclature for in vivo imaging of reversibly binding radioligands.

An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.