Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls!

The observation that amyloid radiotracers developed for Alzheimer's disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination.

In vivo biased agonism at 5-HT receptors: characterisation by simultaneous PET/MR imaging.

In neuropharmacology, the recent concept of 'biased agonism' denotes the capacity of certain agonists to target-specific intracellular pathways of a given receptor in specific brain areas. In the context of serotonin pharmacotherapy, 5-HT receptor-biased agonists could be of great interest in several neuropsychiatric disorders. The aim of this study was to determine whether biased agonists could be differentiated in terms of regional targeting by use of simultaneous functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) brain imaging.

Differential effects of amyloid-beta 1-40 and 1-42 fibrils on 5-HT1A serotonin receptors in rat brain.

Evidence accumulates suggesting a complex interplay between neurodegenerative processes and serotonergic neurotransmission. We have previously reported an overexpression of serotonin 5-HT1A receptors (5-HT(1A)R) after intrahippocampal injections of amyloid-beta 1-40 (Aβ40) fibrils in rats. This serotonergic reactivity paralleled results from clinical positron emission tomography studies with [(18)F]MPPF revealing an overexpression of 5-HT(1A)R in the hippocampus of patients with mild cognitive impairment.

Imaging Dopamine and Serotonin Systems on MPTP Monkeys: A Longitudinal PET Investigation of Compensatory Mechanisms.

Unlabelled: It is now widely accepted that compensatory mechanisms are involved during the early phase of Parkinson's disease (PD) to delay the expression of motor symptoms. However, the neurochemical mechanisms underlying this presymptomatic period are still unclear. Here, we measured in vivo longitudinal changes of both the dopaminergic and serotonergic systems in seven asymptomatic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated monkeys (when motor symptoms are less apparent) using PET.

A microPET comparison of the effects of etifoxine and diazepam on [(11)C]flumazenil uptake in rat brains.

Using positron emission tomography (PET), the present study assessed the binding of [(11)C]flumazenil to GABA-A receptors in anesthetized rats following a single intravenous injection of an active dose of either etifoxine (25mg/kg) or diazepam (1mg/kg), which are both anxiolytic drugs. [(11)C]flumazenil binding was measured in five discrete brain structures, namely the caudate putamen, hippocampus, cerebellum, occipital cortex and parietal cortex. As expected, diazepam injection produced a significant decrease in [(11)C]flumazenil binding, which was interpreted as benzodiazepine GABA-A receptor occupancy, whereas etifoxine increased the binding of [(11)C]flumazenil.

Behavioural impact of a double dopaminergic and serotonergic lesion in the non-human primate.

Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this 5-HT injury-besides the dopaminergic one in the parkinsonian symptomatology-we developed a new monkey model exhibiting a double dopaminergic/serotonergic lesion by sequentially using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3,4-methylenedioxy-N-methamphetamine (MDMA, better known as ecstasy). By positron emission tomography imaging and immunohistochemistry, we demonstrated that MDMA injured 5-HT nerve terminals in the brain of MPTP monkeys.

Ventricular muscarinic receptor remodeling in patients with and without primary ventricular fibrillation. An imaging study.

Background: Vagal innervation modulates the electrical stability of the left ventricle (LV) during ischemia. Thus, abnormal parasympathetic activity in myocardial infarction (MI) patients with primary ventricular fibrillation (FV) can account for their arrhythmic disorders. We evaluated LV muscarinic receptor density (B (max)) after MI in patients with (FV(G), n = 11) or without (nFV(G), n = 12) primary FV.

Muscarinic receptor upregulation in patients with myocardial infarction: a new paradigm.

Background: Despite the major role attributed to myocardial vagal activity in left ventricular arrhythmogenesis in chronic myocardial infarction, the impact of infarction on left ventricular muscarinic receptor density remains unknown.

Methods And Results: Left ventricular muscarinic receptor density was measured in vivo by positron emission tomography using the specific antagonist [(11)C]methylquinuclidinyl benzilate ([(11)C]MQNB) in 11 patients 43+/-20 days after myocardial infarction and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced MRI.

Automated radiosynthesis of the Pittsburg compound-B using a commercial synthesizer.

Background: The Pittsburgh compound-B ([11C]PIB) is a highly interesting radiotracer for imaging amyloid plaques in Alzheimer's disease by positron emission tomography (PET). An increasing number of PET centres schedule its transfer for clinical studies and therefore are interested in its automated synthesis.

Method: With the aim of flexibility, we reported the first fully automated synthesis of [11C]PIB with the coupling of two commercial synthesizers.

Validation of renal oxidative metabolism measurement by positron-emission tomography.

Either in research or in clinical practice, the exploration of renal oxidative metabolism is limited by the lack of noninvasive measurement. Positron-emission tomography using carbon-11 acetate may estimate tissue oxidative metabolism by measuring acetate turnover in the Krebs cycle. Although extensively studied in cardiology, this method has never been validated for renal oxidative metabolism measurement.

Striatal dopamine during sensorial stimulations: a [18F]FDOPA PET study in human and cats.

Sensory stimulations of the forelimb in cats are known to increase dopamine release in the ipsilateral striatum and to decrease it in the homologous contralateral structure. Using positron emission tomography in both humans and cats, the present study shows that such sensory stimulations greatly reduce [(18)F]FDOPA accumulation ipsilateral to the stimulation (by 40.4% and 26.

Seizure-related short-term plasticity of benzodiazepine receptors in partial epilepsy: a [11C]flumazenil-PET study.

We have undertaken a test-re-test [11C]flumazenil (FMZ) PET study in 10 drug-resistant epileptic patients, including six with a mesiotemporal epilepsy (MTE), and 10 normal controls, in order to investigate seizure-related short-term plasticity of benzodiazepine (BZD) receptors. All subjects underwent two FMZ-PET scans at a 1 week interval. Patients benefited from a concurrent video-EEG monitoring which allowed determination of the duration of the interictal period (IP) preceding each PET.

Effect of sensory stimulus on striatal dopamine release in humans and cats: a [(11)C]raclopride PET study.

Background: Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain.

Objectives: To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [(11)C]raclopride. Experiments in humans were paralleled by experiments in anesthetized cats.

PET study of the [11C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow.

Cats were trained to stay in a containment box, without developing any signs of behavioural stress, while their head was maintained in a position that allowed positron emission tomography (PET) experiments to be performed. The binding potential for [(11)C]raclopride (BP(raclo)), a radioligand with good specificity for dopamine (DA) receptors of the D(2) type, was measured in the striatum and in three experimental situations: awake, anaesthetised with ketamine (50 mg kg(-1) h(-1); i.m.

SIC, an intracerebral beta(+)-range-sensitive probe for radiopharmacology investigations in small laboratory animals: binding studies with (11)C-raclopride.

Unlabelled: Our aim was to show the ability of a recently developed beta(+)-range-sensitive intracerebral probe (SIC) to measure, in vivo, the binding of radioligands in small animals.

Methods: The potential of the device for pharmacokinetic studies was evaluated by measurement of the dynamic striatal binding of (11)C-raclopride, a well-documented D(2) dopaminergic receptor ligand, in rat brain after intravenous injection of the labeled compound. The effects of preinjection of the unlabeled ligand (raclopride, 2 mg/kg intravenously) and of increasing the synaptic dopamine level (amphetamine treatment, 1 mg/kg intravenously) or of depleting synaptic dopamine (reserpine pretreatment, 5 mg/kg intraperitoneally) on in vivo (11)C-raclopride binding were monitored by SIC.

The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson's disease.

The contribution of striatal (caudate nucleus-putamen) dopaminergic deficiency to the severity of motor signs is well established in Parkinson's disease (PD), while its role in the occurrence of cognitive and mood changes remains unresolved. We therefore measured in 27 non-demented PD patients and 10 age-matched controls striatal uptake of [18F]-6-fluoro-L-Dopa (F-Dopa) with PET, and mood (Beck depression), memory (Grober-Buschke), frontal executive functions (verbal fluency and Wisconsin card sorting), and attentional processing of sensory stimuli (N2-P3 auditory event-related potentials--ERPs). Locomotor disability of patients was assessed by Hoehn and Yahr score and Unified Parkinson's Disease Rating Scale (UPDRS).

Positron emission tomography during motor cortex stimulation for pain control.

We studied regional changes in cerebral flood flow (rCBF) in 9 patients undergoing motor cortex stimulation (MCS) for pain control. Significant increase in rCBF was observed in the lateral thalamus ipsilateral to MCS probably reflecting corticothalamic connections from motor/premotor areas. Subsignificant increases were observed in the anterior cingulate, left insula and upper brainstem.