[F]RS-127445 radiosynthesis and evaluation as a 5-HT receptor PET radiotracer in rat brain.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter involved in many physiological and pathological mechanisms through its numerous receptors. Among these, the 5-HT receptor is known to play a key role in multiple brain disorders but remains poorly understood. Positron emission tomography (PET) can contribute to a better understanding of pathophysiological mechanisms regulated by the 5-HT receptor.

Preclinical investigation of the effect of stress on the binding of [F]F13640, a 5-HT radiopharmaceutical.

Background: [F]F13640 is a new PET radiopharmaceutical for brain molecular imaging of serotonin 5-HT receptors. Since we intend to use this radiopharmaceutical in psychiatric studies, it is crucial to establish possible sensitivity modification of 5-HT receptors availability during an acute stress exposure. In this study, we first assessed the cerebrometabolic effects of a new animal model of stress with [F]FDG and then proceeded to test for effects of this model on the cerebral binding of [F]F13640, a 5-HT receptors PET radiopharmaceutical.

GABAergic inhibition shapes behavior and neural dynamics in human visual working memory.

Neuronal inhibition, primarily mediated by GABAergic neurotransmission, is crucial for brain development and healthy cognition. Gamma-aminobutyric acid concentration levels in sensory areas have been shown to correlate with hemodynamic and oscillatory neuronal responses. How these measures relate to one another during working memory, a higher-order cognitive process, is still poorly understood.

Deep-learning predicted PET can be subtracted from the true clinical fluorodeoxyglucose PET co-registered to MRI to identify the epileptogenic zone in focal epilepsy.

Objective: Normal interictal [ F]FDG-PET can be predicted from the corresponding T1w MRI with Generative Adversarial Networks (GANs). A technique we call SIPCOM (Subtraction Interictal PET Co-registered to MRI) can then be used to compare epilepsy patients' predicted and clinical PET. We assessed the ability of SIPCOM to identify the Resection Zone (RZ) in patients with drug-resistant epilepsy (DRE) with reference to visual and statistical parametric mapping (SPM) analysis.

Single subanesthetic dose of ketamine produces delayed impact on brain [F]FDG PET imaging and metabolic connectivity in rats.

Introduction: Ketamine, a glutamate NMDA receptor antagonist, is suggested to act very rapidly and durably on the depressive symptoms including treatment-resistant patients but its mechanisms of action remain unclear. There is a requirement for non-invasive biomarkers, such as imaging techniques, which hold promise in monitoring and elucidating its therapeutic impact.

Methods: We explored the glucose metabolism with [F]FDG positron emission tomography (PET) in ten male rats in a longitudinal study designed to compare imaging patterns immediately after acute subanaesthetic ketamine injection (i.

CERMEP-IDB-MRXFDG: a database of 37 normal adult human brain [F]FDG PET, T1 and FLAIR MRI, and CT images available for research.

We present a database of cerebral PET FDG and anatomical MRI for 37 normal adult human subjects (CERMEP-IDB-MRXFDG). Thirty-nine participants underwent static [F]FDG PET/CT and MRI, resulting in [F]FDG PET, T1 MPRAGE MRI, FLAIR MRI, and CT images. Two participants were excluded after visual quality control.

Change in Expression of 5-HT6 Receptor at Different Stages of Alzheimer's Disease: A Postmortem Study with the PET Radiopharmaceutical [18F]2FNQ1P.

Background: The 5-HT6 receptor is one of the most recently identified serotonin receptors in the central nervous system. Because of its role in memory and cognitive process, this receptor might be implicated in Alzheimer's disease (AD) and associated disorders.

Objective: The aim of this study was to investigate the binding of [18F]2FNQ1P, a new specific radiotracer of 5-HT6 receptors, and to quantify 5-HT6 receptor density in caudate nucleus in a population of patients with different AD stages.

Preclinical validation of [F]2FNQ1P as a specific PET radiotracer of 5-HT receptors in rat, pig, non-human primate and human brain tissue.

Introduction: The aim of this study was to perform in-vitro and in-vivo radiopharmacological characterizations of [F]2FNQ1P, a new PET radiotracer of 5-HT receptors, in rat, pig, non-human primate and human tissues. The 5-HT receptor is one of the more recently identified serotonin receptors in central nervous system and, because of its role in memory and cognitive processes, is considered as a promising therapeutic target.

Methods: In-vitro autoradiography and saturation binding assays were performed in postmortem brain tissues from rat, pig, non-human primate and human caudate nucleus, completed by serum stability assessment in all species and cerebral radiometabolite and biodistribution studies in rat.

The predictive value of hypometabolism in focal epilepsy: a prospective study in surgical candidates.

Purpose: FDG PET is an established tool in presurgical epilepsy evaluation, but it is most often used selectively in patients with discordant MRI and EEG results. Interpretation is complicated by the presence of remote or multiple areas of hypometabolism, which leads to doubt as to the true location of the seizure onset zone (SOZ) and might have implications for predicting the surgical outcome. In the current study, we determined the sensitivity and specificity of PET localization prospectively in a consecutive unselected cohort of patients with focal epilepsy undergoing in-depth presurgical evaluation.

Cognitive Deficits and Inflammatory Response Resulting from Mild-to-Moderate Traumatic Brain Injury in Rats Are Exacerbated by Repeated Pre-Exposure to an Innate Stress Stimulus.

Traumatic brain injury (TBI) is common in both military and civilian populations, and often results in neurobehavioral sequelae that impair quality of life in both patients and their families. Although individuals who are chronically exposed to stress are more likely to experience TBI, it is still unknown whether pre-injury stress influences the outcome after TBI. The present study tested whether behavioral and cognitive long-term outcome after TBI in rats is affected by prior exposure to an innate stress stimulus.

Correlation of FDG-PET hypometabolism and SEEG epileptogenicity mapping in patients with drug-resistant focal epilepsy.

Objective: Interictal [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is used in the presurgical evaluation of patients with drug-resistant focal epilepsy. We aimed at clarifying its relationships with ictal high-frequency oscillations (iHFOs) shown to be a relevant marker of the seizure-onset zone.

Methods: We studied the correlation between FDG-PET and epileptogenicity maps in an unselected series of 37 successive patients having been explored with stereo-electroencephalography (SEEG).

Gamma oscillations in V1 are correlated with GABA(A) receptor density: A multi-modal MEG and Flumazenil-PET study.

High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition.

Can we increase the yield of FDG-PET in the preoperative work-up for epilepsy surgery?

Purpose: [(18)F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a semi-invasive, interictal method of localization of hypometabolic epileptic foci. FDG-PET can be useful in the clinical work-up prior to epilepsy surgery, especially in equivocal cases. We investigated whether we could increase the yield of presurgical FDG-PET in patients with difficult epilepsy requiring chronic subdural electrocorticography (ECoG).

Accuracy of distinguishing between dysembryoplastic neuroepithelial tumors and other epileptogenic brain neoplasms with [¹¹C]methionine PET.

Background: Dysembryoplastic neuroepithelial tumors (DNTs) represent a prevalent cause of epileptogenic brain tumors, the natural evolution of which is much more benign than that of most gliomas. Previous studies have suggested that [(11)C]methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumors, and hence optimize the management of patients. Here, we reassessed the diagnostic accuracy of MET-PET for the differentiation between DNT and other epileptogenic brain neoplasms in a larger population.

Positron emission tomography with α-[11C]methyl-L-tryptophan in tuberous sclerosis complex-related epilepsy.

Objective: Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α-[(11) C]methyl-l-tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity.

Methods: We included 12 patients (six male, 4-53 years old) with TSC and refractory seizures who were evaluated for epilepsy surgery in our center, including video-electroencephalographic (EEG) monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI), and positron emission tomography (PET) with α-[(11) C]methyl-l-tryptophan (AMT-PET).

Periventricular [(11)C]flumazenil binding for predicting postoperative outcome in individual patients with temporal lobe epilepsy and hippocampal sclerosis.

A third of patients with intractable temporal lobe epilepsy and hippocampal sclerosis (HS) are not seizure free (NSF) after surgery. Increased periventricular [(11)C]flumazenil (FMZ) binding, reflecting heterotopic neuron concentration, has been described as one predictor of NSF outcome at the group level. We aimed to replicate this finding in an independent larger cohort and investigated whether NSF outcome can be predicted in individuals.

A phantom and animal study of temperature changes during fMRI with intracerebral depth electrodes.

Background: MRI is routinely used in patients undergoing intracerebral electroencephalography (icEEG) in order to precisely locate the position of intracerebral electrodes. In contrast, fMRI has been considered unsafe due to suspected greater risk of radiofrequency-induced (RF) tissue heating at the vicinity of intracerebral electrodes. We determined the possible temperature change at the tip of such electrodes during fMRI sessions in phantom and animals.

Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage), which offers: (1) minimally stressful social interactions; (2) increased voluntary exercise; (3) multiple entertaining activities; (4) cognitive stimulation (maze exploration), and (5) novelty (maze configuration changed three times a week).

Effects of aripiprazole, risperidone, and olanzapine on 5-HT1A receptors in patients with schizophrenia.

To investigate the impact of various antipsychotic drugs on the 5-HT1A serotoninergic system, we performed a [F]4-(2-methoxyphenyl)-1-[2-(N-2-pirydynyl)-p-luorobenzamido]-ethyl-piperazine PET study in 19 schizophrenic patients treated with either aripiprazole, which has a partial agonist activity at 5-HT1A receptors, or second-generation antipsychotics (SGA) (olanzapine or risperidone), which do not demonstrate such property. We used a simplified reference tissue model to generate parametric images of [F]MPPF-binding potential (BPND). A significant reduction of [F]MPPF BPND was found in treated schizophrenic patients compared to age- and sex-matched healthy subjects.

5-HT(1A) receptor binding changes in patients with major depressive disorder before and after antidepressant treatment: a pilot [¹⁸F]MPPF positron emission tomography study.

This is the first [¹⁸F]MPPF PET study in positron emission tomography study in depressed patients, both before and after treatment with a selective serotonin reuptake inhibitor (SSRI). Dynamic changes in [¹⁸F]MPPF binding potential were observed primarily in the medial orbital regions from baseline to 30 days of treatment, suggesting SSRI-mediated serotoninergic adaptative mechanisms.

Voxel-based analysis of asymmetry index maps increases the specificity of 18F-MPPF PET abnormalities for localizing the epileptogenic zone in temporal lobe epilepsies.

Unlabelled: (18)F-4-(2'-methoxyphenyl)-1-[2'-(N-2-pyridinyl)-p-fluorobenzamido]-ethyl-piperazine ((18)F-MPPF) PET has proved to be a sensitive technique in the presurgical evaluation of patients with drug-resistant temporal lobe epilepsy (TLE), but a significant proportion of visually detected abnormalities failed to be detected by standard statistical parametric mapping (SPM) analysis. This study aimed at describing a voxel-based method for computing interhemispheric asymmetric index (AI) using statistical software and applying and validating the clinical relevance of this method for analyzing asymmetries of (18)F-MPPF PET images in patients with drug-resistant TLE.

Methods: (18)F-MPPF PET scans of 24 TLE patients who achieved an Engel class I outcome after epilepsy surgery and of 41 controls were analyzed visually, with standard SPM, and by computing voxel-based AIs.

5-HT1A gene promoter polymorphism and [18F]MPPF binding potential in healthy subjects: a PET study.

Background: Previous Positron Emission Tomography (PET) studies of 5-HT1A receptors have shown an influence of several genetic factors, including the triallelic serotonin transporter gene-linked polymorphic region on the binding potential (BPND) of these receptors. The aim of our study was to investigate the relationship between a 5-HT1A promoter polymorphism and the binding potential of another selective 5-HT1A receptor antagonist, [18F]MPPF, in healthy subjects.

Methods: Thirty-five volunteers, including 23 women, underwent an [18F]MPPF scan and were genotyped for both the C(-1019)G 5-HT1A promoter polymorphism and the triallelic serotonin transporter gene-linked polymorphic region.