Abstract
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.
Highlights
Monoamine oxidase (MAO) is a mitochondrial enzyme responsible for the degradation of several neurotransmitters, such as dopamine, serotonin, and noradrenaline
Two MAO isoforms - products of different genes - have been identified in mammals: enzyme monoamine oxidase A (MAO-A), which is primarily found in cathecolaminergic neurons, and MAO-B, which is mainly present in glial cells and serotonergic neurons [1]
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]. [11C]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
Summary
Monoamine oxidase (MAO) is a mitochondrial enzyme responsible for the degradation of several neurotransmitters, such as dopamine, serotonin, and noradrenaline. With some exceptions [6], studies on MAO-A activity have been hindered by the lack of suitable ligands for this enzyme. Befloxatone is a potent, selective, and reversible inhibitor of brain MAO-A activity [10]. It can be radiolabeled with 11C using [11C]phosgene as the reagent [11]. [11C] Befloxatone has a highly specific binding to MAO-A, as shown by extensive in vitro [10] and in vivo studies in primates [12]. [11C]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. This paper sought to (1) quantify the uptake of [11C]befloxatone in the human brain, both at the regional and voxel level, using an arterial input function; and (2) explore the possibility of replacing the arterial input function with a less invasive approach based on sampling of arterialized venous blood
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