PEPTIDE CLICK LABELLING WITH 1-(AZIDOMETHYL)-4-[18F]-FLUOROBENZENE AND REFERENCE COMPOUNDS SYNTHESIS ON SOLID SUPPORT

in Journal of Labelled Compounds and Radiopharmaceuticals (2009, July)

Modulation of fMRI assessed brain responses to blue and green light by sleep homeostasis, circadian phase and PER3 polymorphism

Conference (2009, June)

Functional Magnetic Resonance Imaging-Assessed Brain Responses during an Executive Task Depend on Interaction of Sleep Homeostasis, Circadian Phase, and PER3 Genotype

in Journal of Neuroscience (2009), 29

Cognition is regulated across the 24 h sleep-wake cycle by circadian rhythmicity and sleep homeostasis through unknown brain mechanisms. We investigated these mechanisms in a functional magnetic resonance ... [more ▼]

Cognition is regulated across the 24 h sleep-wake cycle by circadian rhythmicity and sleep homeostasis through unknown brain mechanisms. We investigated these mechanisms in a functional magnetic resonance imaging study of executive function using a working memory 3-back task during a normal sleep-wake cycle and during sleep loss. The study population was stratified according to homozygosity for a variable-number (4 or 5) tandem-repeat polymorphism in the coding region of the clock gene PERIOD3. This polymorphism confers vulnerability to sleep loss and circadian misalignment through its effects on sleep homeostasis. In the less-vulnerable genotype, no changes were observed in brain responses during the normal-sleep wake cycle. During sleep loss, these individuals recruited supplemental anterior frontal, temporal and subcortical regions, while executive function was maintained. In contrast, in the vulnerable genotype, activation in a posterior prefrontal area was already reduced when comparing the evening to the morning during a normal sleep-wake cycle. Furthermore, in the morning after a night of sleep loss, widespread reductions in activation in prefrontal, temporal, parietal and occipital areas were observed in this genotype. These differences occurred in the absence of genotype-dependent differences in circadian phase. The data show that dynamic changes in brain responses to an executive task evolve across the sleep-wake and circadian cycles in a regionally specific manner that is determined by a polymorphism which affects sleep homeostasis. The findings support a model of individual differences in executive control, in which the allocation of prefrontal resources is constrained by sleep pressure and circadian phase. [less ▲]

Novel Stealthy Gd(III)-DOTA/polymer Conjugates for Magnetic Resonance Imaging (MRI)

Conference (2009, May 14)

Magnetic resonance imaging (MRI) is a routine diagnostic tool in modern clinical medicine. MRI has many advantages as a diagnostic imaging modality. It is noninvasive, delivers no radiation, and has ... [more ▼]

Magnetic resonance imaging (MRI) is a routine diagnostic tool in modern clinical medicine. MRI has many advantages as a diagnostic imaging modality. It is noninvasive, delivers no radiation, and has excellent (submillimeter) spatial resolution. Some Gadolinium(III) complexes are commonly used to enhance the contrast between adjacent tissues when the resolution/sensitivity of MRI is too low. Because free Gd3+ is very toxic in doses required for MRI, Gd(III) is chelated by poly(amino-carboxylate) such as diethylenetriamine pentaacetic acid (DTPA) or 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Although DTPA/Gd3+ and DOTA/Gd3+ are water soluble, they have a very short circulation lifetime in blood, a low molecular weight and a short rotational time that make the contrast poor. To enhance the contrast, the Gd3+/complex doses have to be increased. In order to increase the sensitivity of the technique, while not increasing the concentration of the contrast agent, we were investigating different strategies to improve (i) the circulation lifetime in blood, (ii) the relaxation rate of Gd(III) (and consequently, the contrasting efficiency) and (iii) the targeting of the contrast agent. This presentation aims at reporting how a multifunctional (co)polymer can be designed and exploited for improving the contrasting ability and bioavailability of gadolinium-based complexes. [less ▲]

Is brain activity during a Stroop inhibitory task modulated by the kind of cognitive control required?

Poster (2009, May 11)

Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging

Poster (2009, March 18)

Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their ... [more ▼]

Click chemistry : radiolabelling of oligonucleotides with fluorine-18 for PET imaging Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their pharmacokinetics and biodistributions are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to image and quantify such biological processes. The challenge for the radiochemist is to introduce this short half-life isotope (t1/2(18F)=109.7 min) onto oligonucleotides or, more generally, biomolecules. The most common technique requires the coupling of a prosthetic group bearing the radiotracer with the biomolecule. Current methods for labeling ONs with fluorine-18 have sub-optimal yields and require a long synthesis time.{Vries2003} Click chemistry, e.g. 1,3-dipolar Huisgen cycloaddition of azides to alkynes, could be an efficient way to increase yields and reduce synthesis time (see Figure 1). This family of reactions are well suited to the radiolabelling of ONs as they are tolerant to a wide range of solvent and require mild reaction conditions and simple purifications.{Glaser2007} The major strength of this approach is its versatility: it can be easily transposed to any other kind of biomolecules (e.g. peptides, lipids) as long as they can bear an azido or alkyne moiety. Conjugations with ONs are usually performed at 3’-ends using a well-chosen linker in order to limit degradation by exonucleases and to avoid alteration of hybridization properties and siRNA gene silencing efficiency.{Kurreck2009} This also allows the development of universal solid support because synthesis occurs from the 3’ to 5’-end. The linker must fulfil a number of requirements:{Gait2001} - Bearing one alkyne, one primary and one secondary alcohol moiety; - Having a well-defined and known stereochemistry. According to these terms, we propose three different potential linkers (see Figure 2) that can be incorporated into the solid-phase synthesis of ONs. Starting materials are commercially available as pure enantiomers at an affordable price. Here we report the synthesis and characterisation of an alkyne-bearing linker and the synthesis and radiosynthesis of the complementary azido-bearing prosthetic groups (1-(azidomethyl)-4-[18F]-fluorobenzene). [less ▲]

Neurobiological bases of suicidality in major depression

in World Journal of Biological Psychiatry (2009), 9(Suppl. 1),

Increased filtering of irrelevant information in obsessive-compulsive disorder (OCD) patient

Poster (2009)

Pain and non-pain processing during hypnosis: a thulium-YAG event-related fMRI study.

in NeuroImage (2009), 47(3), 1047-54

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and ... [more ▼]

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and connectivity related to the hypnotic state as compared to normal wakefulness in 13 healthy volunteers. Behaviorally, a difference in subjective ratings was found between normal wakefulness and hypnotic state for both non-painful and painful intensity-matched stimuli applied to the left hand. In normal wakefulness, non-painful range stimuli activated brainstem, contralateral primary somatosensory (S1) and bilateral insular cortices. Painful stimuli activated additional areas encompassing thalamus, bilateral striatum, anterior cingulate (ACC), premotor and dorsolateral prefrontal cortices. In hypnosis, intensity-matched stimuli in both the non-painful and painful range failed to elicit any cerebral activation. The interaction analysis identified that contralateral thalamus, bilateral striatum and ACC activated more in normal wakefulness compared to hypnosis during painful versus non-painful stimulation. Finally, we demonstrated hypnosis-related increases in functional connectivity between S1 and distant anterior insular and prefrontal cortices, possibly reflecting top-down modulation. [less ▲]

Mécanismes de l'anesthésie générale: apport de l'imagerie fonctionnelle

in Revue Médicale de Liège (2009), 64(Synthèse 2009), 36-41