PET imaging of GABA receptors in pancreatic islets by [C]flumazenil.

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive β-cell destruction. There are no clinically established methods for quantifying endocrine cells of the pancreas and current knowledge is almost exclusively based on autopsy material and functional measurements. Based on the expression of the γ-aminobutyric acid A receptors (GABARs) in pancreatic islets and the fact that GABAR agonists are being explored as treatment for T1D, we hypothesized that the positron emission tomography (PET) tracer [C]flumazenil ([C]FMZ) could serve as a marker of the endocrine mass of the pancreas.

Dental pulp mesenchymal stem cell (DPSCs)-derived soluble factors, produced under hypoxic conditions, support angiogenesis via endothelial cell activation and generation of M2-like macrophages.

Background: Cell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine.

Methods: Here, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors.

Regional distribution of mechanical strain and macrophage-associated lung inflammation after ventilator-induced lung injury: an experimental study.

Background: Alveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages.

Evaluation of [C]UCB-A positron emission tomography in human brains.

Background: In preclinical studies, the positron emission tomography (PET) imaging with [C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [C]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.

Results: Twelve healthy subjects underwent 90-min baseline [C]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg).

Radiation dosimetry of para-chloro-2-[F]fluoroethyl-etomidate: a PET tracer for adrenocortical imaging.

Background: [C]metomidate, a methyl ester analogue of etomidate, is used for positron emission tomography of adrenocortical cancer, and has been tested in recent clinical trials for lateralization in primary aldosteronism (PA). However, in PA, visualization as well as uptake quantification are hampered by the tracer's rather high non-specific liver uptake, and its overall clinical usefulness is also limited by the short 20-minute half-life of carbon-11. Therefore, we evaluated para-chloro-2-[F]fluoroethyl-etomidate, [F]CETO, a fluorine-18 (T=109.

Automated radiosynthesis of [ F]CETO, a PET radiotracer for imaging adrenal glands, on Synthra RNplus.

Primary aldosteronism (PA) is the leading secondary cause of hypertension. Determining whether one (unilateral) or both (bilateral) adrenal glands are the source of PA in a patient remains challenging, and yet it is a critical step in the decision whether to recommend potentially curative surgery (adrenalectomy) or lifelong medical therapy (typically requiring multiple drugs). Recently, we have developed a fluorine-18 radiopharmaceutical [ F]CETO to permit greater access to PA molecular imaging.

Serotonin and dopamine transporter availability in social anxiety disorder after combined treatment with escitalopram and cognitive-behavioral therapy.

Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [C]DASB and [C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively.

PET Imaging of Neutrophil Elastase with C-GW457427 in Acute Respiratory Distress Syndrome in Pigs.

Today, there is a lack of clinically available imaging techniques to detect and quantify specific immune cell populations. Neutrophils are one of the first immune cells at the site of inflammation, and they secrete the serine protease neutrophil elastase (NE), which is crucial in the fight against pathogens. However, the prolonged lifespan of neutrophils increases the risk that patients will develop severe complications, such as acute respiratory distress syndrome (ARDS).

First-in-human evaluation of [F]CETO: a novel tracer for adrenocortical tumours.

Purpose: [C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[F]fluoroethyletomidate has been proven to be a specific adrenal tracer.

Estimating the effect on happiness through question randomization: An application to blood donation.

We rely on the randomized activation of the heuristic of attribute substitution to analyze the effect of blood donation on donors' happiness. We randomly delivered two versions of a questionnaire where the happiness question is alternatively placed immediately before or after a categorical question asking about the blood donor condition of the respondent (non-donor, previously donor, donor). By comparing the answers given to the happiness question in the two versions, we find a positive effect of donating blood on donors' happiness.

Chronic cerebral blood flow alterations in traumatic brain injury and sports-related concussions.

Primary Objective: Traumatic brain injury (TBI) and sports-related concussion (SRC) may result in chronic functional and neuroanatomical changes. We tested the hypothesis that neuroimaging findings (cerebral blood flow (CBF), cortical thickness, and H-magnetic resonance (MR) spectroscopy (MRS)) were associated to cognitive function, TBI severity, and sex.

Research Design: Eleven controls, 12 athletes symptomatic following ≥3SRCs and 6 patients with moderate-severe TBI underwent MR scanning for evaluation of cortical thickness, brain metabolites (MRS), and CBF using pseudo-continuous arterial spin labeling (ASL).

In Vivo Visualization and Quantification of Neutrophil Elastase in Lungs of COVID-19 Patients: A First-in-Humans PET Study with C-NES.

Coronavirus disease 2019 (COVID-19) can cause life-threatening lung inflammation that is thought to be mediated by neutrophils. The aim of the present work was to evaluate a novel PET tracer for neutrophil elastase (NE). In this first-in-humans study, 4 patients with hypoxia due to COVID-19 and 2 healthy controls were investigated with PET using C-NES and O-water for visualization and quantification of NE and perfusion in the lungs, respectively.

The synthesis of soluble and volatile bioactive compounds by selected brewer's yeasts: Antagonistic effect against enteropathogenic bacteria and food spoiler - toxigenic sp.

Contamination by sp. and the accumulation of its mycotoxins in food and beverages have a high impact on human health and food safety. This investigation inquires the ability of brewer's yeasts discarded after fermentation (brewing fermentation residue, BFR) to synthesize bioactive compounds and to biocontrol sp.

E-Cigarette Aerosol Deposition and Disposition of [C]Nicotine Using Positron Emission Tomography: A Comparison of Nicotine Uptake in Lungs and Brain Using Two Different Nicotine Formulations.

Smoking is a cause of serious disease in smokers. Electronic cigarettes, delivering aerosolized nicotine, offer adult smokers a potentially less harmful alternative to combustible cigarettes. This explorative PET/CT study investigated the distribution and deposition of inhaled [C]nicotine using the blu e-cigarette with two nicotine formulations, freebase and lactate salt.

Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study.

Background: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis.

Methods: Both were uncontrolled open-label studies.

Cardiac microcalcifications in transthyretin (ATTR) amyloidosis.

Background: Bone tracers bind to amyloid-containing heart of most patients with ATTR amyloidosis. Amyloid deposits outside the heart are often scarce and bone scintigraphy is increasingly often used to diagnose cardiac involvement. However, the nature of the binding of bone tracers to the heart is not clear.

Preclinical evaluation of [C]GW457427 as a tracer for neutrophil elastase.

Introduction: Neutrophils are part of the innate immune system and function as a first line of defense against invading microorganisms. Overactivity of the immune system may result in a devastating immuno-inflammation with extensive damage to tissue leading to organ damage and/or failure. The literature suggests several human diseases in which neutrophil elastase (NE) is postulated to be important in the pathophysiology including inflammatory bowel disease (IBD), chronic obstructive pulmonary disorder (COPD), abdominal aortic aneurysms (AAA), breast and lung cancer, and recently also in Sars-cov-2 virus infection (Covid-19).

Refined Analysis of Chronic White Matter Changes after Traumatic Brain Injury and Repeated Sports-Related Concussions: Of Use in Targeted Rehabilitative Approaches?

Traumatic brain injury (TBI) or repeated sport-related concussions (rSRC) may lead to long-term memory impairment. Diffusion tensor imaging (DTI) is helpful to reveal global white matter damage but may underestimate focal abnormalities. We investigated the distribution of post-injury regional white matter changes after TBI and rSRC.

Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial.

It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment.

Improved Radiolytic Stability of a Ga-labelled Collagelin Analogue for the Imaging of Fibrosis.

There is an unmet medical need for non-invasive, sensitive, and quantitative methods for the assessment of fibrosis. Herein, an improved collagelin analogue labelled with gallium-68 for use with positron emission tomography (PET) is presented. A cyclic peptide, c[CPGRVNleHGLHLGDDEGPC], was synthesized by solid-phase peptide synthesis, conjugated to 2-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazonan-1-yl)acetic acid, and labelled with gallium-68.

Risk factors for HIV infection among men who have sex with men in the ANRS IPERGAY PrEP trial.

Objectives: We aimed to assess among men who have sex with men (MSM) risk factors for HIV infection, to identify those who require urgent pre-exposure prophylaxis (PrEP) prescription.

Methods: All participants enrolled in the placebo arm of the ANRS IPERGAY trial, or infected between screening and day 0, were included. Baseline characteristics were described and HIV incidence rate ratios (RRs) were estimated with their 95% CIs.

Glucagonlike Peptide-1 Receptor Imaging in Individuals with Type 2 Diabetes.

The glucagonlike peptide-1 receptor (GLP1R) is a gut hormone receptor, intricately linked to regulation of blood glucose homeostasis via several mechanisms. It is an established and emergent drug target in metabolic disease. The PET radioligand Ga-DO3A-VS-exendin4 (Ga-exendin4) has the potential to enable longitudinal studies of GLP1R in the human pancreas.