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

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.

11CO bonds made easily for positron emission tomography radiopharmaceuticals

“…124 Indeed, [ 11 C- methyl ]befloxatone is currently used in human imaging research. 125 As discussed earlier, reversible oxazolidinone MAO-B radioligands [ 11 C]SBox-13 and [ 11 C]SL25.1188 were originally developed using [ 11 C]COCl 2 , 79,126,127 but improvements in the synthesis of the latter compound using [ 11 C]CO 2 -fixation have enabled human translation (Fig. 3).…”

Detection of monoamine oxidase a in brain of living rats with [18F]fluoroethyl‐harmol PET

“…In contrast, the cerebral binding to MAO‐A of [ 11 C]clorgyline is difficult to quantify since the rate constant for irreversible binding is so very high, and due to the presence of a nonspecific binding component in white matter (Fowler et al, ). Other reversibly binding PET ligands for MAO‐A include [ 11 C]befloxatone (Zanotti‐Fregonara et al, ) and [ 11 C]ROMAO (Jensen et al, ). However, only [ 11 C]harmine is currently finding use in human PET studies of brain MAO‐A (Chiuccariello et al, ).…”

Deriving physiological information from PET images: from SUV to compartmental modelling

“…SA has been applied to preclinical (rats and rabbits) [44,45] as well as to clinical data. Most of its applications are related to the investigation of brain neuroreceptors [39,[46][47][48] or enzymes [49,50] even though SA has also been applied to PET studies involving the heart [51], skeletal leg muscle [52,53], breast cancer [54] and gastrointestinal cancer [55]. Most of these applications aimed to exploit spectral-based procedures to overcome the limits of the standard quantification methodologies.…”