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The recent introduction of a number of new radiotracers suitable for imaging the serotonin transporters (SERT) has radically changed the field of SERT imaging. Whereas, until recently, only one selective SERT radiotracer was available ([ 11 C]McN 5652) for SERT imaging with positron emission tomography (PET), several new C-11-labeled radiotracers of the N,N-dimethyl-2-(arylthio)benzylamine class have been described as appropriate imaging agents for the SERT. The aim of this study was to conduct a comparative evaluation of four of the most promising agents in this class ([ 11 C]ADAM, [ 11 C]DASB, [ 11 C]DAPA, and [ 11 C]AFM) with the reference tracer [ 11 C]McN 5652 under standardized experimental conditions. This evaluation included in vitro measurements of affinity and lipophilicity, and in vivo PET imaging experiments in baboons. In vitro, DASB displayed significantly lower affinity for SERT than the other four tracers. In the blood, [ 11 C]DASB and [ 11 C]AFM display faster clearance and higher free fractions. Brain uptake was analyzed with kinetic modeling using a one-tissue compartment model and the metabolite-corrected arterial input function. The kinetic uptake of [ 11 C]DASB was significantly faster compared with the other compounds, and the scan duration required to derive time-independent estimates of regional distribution volumes was shorter. [ 11 C]DAPA exhibited the slowest brain kinetic. Regional-specific-to-nonspecific equilibrium partition coefficient (V 3 “) was the highest for [ 11 C]AFM, followed by [ 11 C]DASB and [ 11 C]DAPA, which in turn provided higher V 3 ” values than [ 11 C]ADAM and [ 11 C]McN 5652. From these experiments, two ligands emerged as superior radiotracers that provide a significant improvement over [ 11 C]McN 5652 for PET imaging of SERT: [ 11 C]DASB, because it enables the measurement of SERT availability in a shorter scanning time, and [ 11 C]AFM, because its higher signal-to-noise ratios provide a more reliable measurement of SERT availability in brain regions with relatively low density of SERT, such as in the limbic system.

journal of cerebral blood flow and metabolism

Comparative Evaluation in Nonhuman Primates of Five PET Radiotracers for Imaging the Serotonin Transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM