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

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 (V_T) values of [¹¹C]befloxatone in humans using an arterial input function. Methods: Seven 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. Results: An unconstrained two-compartment model reliably quantified V_T values in large brain regions. A constrained model did not significantly improve V_T identifiability. Similar V_T results were obtained using SA; however, the Logan plot and MA1 slightly underestimated V_T values (about -10%). At the voxel level, SA showed a very small bias (+2%) compared to compartmental modeling, Logan severely underestimated V_T 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-V_T regional values were not comparable to those obtained with arterial sampling in all subjects. Conclusions: Binding 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.