Mapping the Cerebral Monoamine Oxidase Type A: Positron Emission Tomography Characterization of the Reversible Selective Inhibitor [<sup>11</sup>C]Befloxatone

Bottlaender, Michel; Dollé, Frédéric; Guenther, Ilonka; Roumenov, Dimitri; Fuseau, Chantal; Bramoullé, Yann; Curet, O.; Jegham, Jamir; Pinquier, Jean‐Louis; George, Pascal; Valette, Héric

doi:10.1124/jpet.102.046953

Cited by 31 publications

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“…The MAO activity was estimated using a new reversible and selective radioligand of MAO-A isoenzyme, [ 11 C]befloxatone, which penetrates easily the blood-brain barrier and accumulates rapidly in the brain. 4,5 The aim of this study was to confirm the earlier reported 3 smoking-associated reduction of MAO-A sites availability.…”

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confidence: 55%

Cerebral Monoamine Oxidase A Inhibition in Tobacco Smokers Confirmed With PET and [11C]Befloxatone

Leroy¹,

Bragulat²,

Berlin³

et al. 2009

Journal of Clinical Psychopharmacology

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The inhibition of cerebral monoamine oxidases (MAOs) by cigarette smoke components could participate to the tobacco addiction. However, the actual extent of this inhibition in vivo in smokers is still poorly known. We investigated cerebral MAO-A availability in 7 tobacco-dependent subjects and 6 healthy nonsmokers, using positron emission tomography (PET) and the MAO-A selective radioligand [C]befloxatone. In comparison to nonsmokers, smokers showed a significant overall reduction of [C]befloxatone binding potential (BP) in cortical areas (average reduction, -60%) and a similar trend in caudate and thalamus (-40%). Our findings confirm a widespread inhibition of cerebral MAO-A in smokers. This mechanism may contribute to tobacco addiction and for a possible mood-modulating effect of tobacco.

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confidence: 55%

Cerebral Monoamine Oxidase A Inhibition in Tobacco Smokers Confirmed With PET and [11C]Befloxatone

Leroy¹,

Bragulat²,

Berlin³

et al. 2009

Journal of Clinical Psychopharmacology

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“…The most successful ligands which have been validated in humans are [ 11 C]harmine (e.g., Bergström et al 1997;Ginovart et al 2006;Jensen et al 2006;Soliman et al 2011), [ 11 C]clorgyline and [ 11 C]clorgyline-D2 (Fowler et al 1987Logan et al 2002) and [ 11 C]befloxatone (Bottlaender et al 2003;Leroy et al 2009). Another promising carbonlabeled PET ligand, …”

Section: Monoamine Oxidase Type a (Mao-a)mentioning

confidence: 99%

Serotonin and molecular neuroimaging in humans using PET

2011

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The serotonergic system is one of the most important modulatory neurotransmitter systems in the human brain. It plays a central role in major physiological processes and is implicated in a number of psychiatric disorders. Along with the dopaminergic system, it is also one of the phylogenetically oldest human neurotransmitter systems and one of the most diverse, with 14 different receptors identified up to this day, many of whose function remains to be understood. The system's functioning is even more diverse than the number of its receptors, since each is implicated in a number of different processes. This review aims at illustrating the distribution and summarizing the main functions of the serotonin (5-hydroxytryptamin, 5-HT) receptors as well as the serotonin transporter (SERT, 5-HTT), the vesicular monoamine transporter 2, monoamine oxidase type A and 5-HT synthesis in the human brain. Recent advances in in vivo quantification of these different receptors and enzymes that are part of the serotonergic system using positron emission tomography are described.

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“…It can be radiolabeled with 11 C using [ 11 C]phosgene as the reagent [11]. [ 11 C]Befloxatone has a highly specific binding to MAO-A, as shown by extensive in vitro [10] and in vivo studies in primates [12]. In particular, nonsaturable uptake, obtained after a pretreatment with a high dose of unlabeled befloxatone, is very low and represents only 3% of the total uptake [12].…”

Section: Introductionmentioning

confidence: 99%

“…[ 11 C]Befloxatone has a highly specific binding to MAO-A, as shown by extensive in vitro [10] and in vivo studies in primates [12]. In particular, nonsaturable uptake, obtained after a pretreatment with a high dose of unlabeled befloxatone, is very low and represents only 3% of the total uptake [12]. [ 11 C]Befloxatone has good imaging characteristics and has been used in positron emission tomography (PET) studies to quantify in vivo MAO-A in rats [13], nonhuman primates [12,14], and humans.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, nonsaturable uptake, obtained after a pretreatment with a high dose of unlabeled befloxatone, is very low and represents only 3% of the total uptake [12]. [ 11 C]Befloxatone has good imaging characteristics and has been used in positron emission tomography (PET) studies to quantify in vivo MAO-A in rats [13], nonhuman primates [12,14], and humans. In humans, it has been used to compare MAO-A binding potential in smokers and nonsmokers [7]; however, a rigorous kinetic modeling study in humans has never been performed.…”

Section: Introductionmentioning

confidence: 99%

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Kinetic analysis of [11C]befloxatone in the human brain, a selective radioligand to image monoamine oxidase A

et al. 2013

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Background[11C]Befloxatone measures the density of the enzyme monoamine oxidase A (MAO-A) in the brain. MAO-A is responsible for the degradation of different neurotransmitters and is implicated in several neurologic and psychiatric illnesses. This study sought to estimate the distribution volume (VT) values of [11C]befloxatone in humans using an arterial input function.MethodsSeven healthy volunteers were imaged with positron emission tomography (PET) after [11C]befloxatone injection. Kinetic analysis was performed using an arterial input function in association with compartmental modeling and with the Logan plot, multilinear analysis (MA1), and standard spectral analysis (SA) at both the regional and voxel level. Arterialized venous samples were drawn as an alternative and less invasive input function.ResultsAn unconstrained two-compartment model reliably quantified VT values in large brain regions. A constrained model did not significantly improve VT identifiability. Similar VT results were obtained using SA; however, the Logan plot and MA1 slightly underestimated VT values (about -10%). At the voxel level, SA showed a very small bias (+2%) compared to compartmental modeling, Logan severely underestimated VT values, and voxel-wise images obtained with MA1 were too noisy to be reliably quantified. Arterialized venous blood samples did not provide a satisfactory alternative input function as the Logan-VT regional values were not comparable to those obtained with arterial sampling in all subjects.ConclusionsBinding of [11C]befloxatone to MAO-A can be quantified using an arterial input function and a two-compartment model or, in parametric images, with SA.

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Mapping the Cerebral Monoamine Oxidase Type A: Positron Emission Tomography Characterization of the Reversible Selective Inhibitor [¹¹C]Befloxatone

Cited by 31 publications

References 30 publications

Cerebral Monoamine Oxidase A Inhibition in Tobacco Smokers Confirmed With PET and [11C]Befloxatone

Cerebral Monoamine Oxidase A Inhibition in Tobacco Smokers Confirmed With PET and [11C]Befloxatone

Serotonin and molecular neuroimaging in humans using PET

Kinetic analysis of [11C]befloxatone in the human brain, a selective radioligand to image monoamine oxidase A

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Mapping the Cerebral Monoamine Oxidase Type A: Positron Emission Tomography Characterization of the Reversible Selective Inhibitor [11C]Befloxatone

Cited by 31 publications

References 30 publications

Cerebral Monoamine Oxidase A Inhibition in Tobacco Smokers Confirmed With PET and [11C]Befloxatone

Cerebral Monoamine Oxidase A Inhibition in Tobacco Smokers Confirmed With PET and [11C]Befloxatone

Serotonin and molecular neuroimaging in humans using PET

Kinetic analysis of [11C]befloxatone in the human brain, a selective radioligand to image monoamine oxidase A

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Mapping the Cerebral Monoamine Oxidase Type A: Positron Emission Tomography Characterization of the Reversible Selective Inhibitor [¹¹C]Befloxatone