Quantification of 11C-MADAM Binding to the Serotonin Transporter in the Human Brain

Journal of Nuclear Medicine

Ikuo Odano¹  Johan Lundberg¹  Christer Halldin¹  Hans Olsson¹  Lars Farde¹ 

关键词: brain;    humans;    serotonin transporter;    serotonin;    PET;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

11C-N,N-Dimethyl-2-(2-amino-4-methylphenylthio)benzylamine (11C-MADAM) is a newly synthesized radioligand with high selectivity and specificity for the serotonin transporter (5-HTT) in a monkey model. The purpose of this study in humans was to examine the suitability and potential of 11C-MADAM for quantitative PET studies of 5-HTT in applied clinical studies on the pathophysiology and treatment of neuropsychiatric disorders. Methods: PET examination was performed on each of 9 male subjects after intravenous injection of 11C-MADAM with high specific radioactivity. Radioactive metabolites in plasma were determined with high-performance liquid chromatography. A metabolite-corrected arterial input function was used in kinetic 2- and 3-compartment analyses. Cerebellum was used as the reference region in a cross-validation of 6 reference tissue approaches. Results: The highest radioactivity concentration was detected in the raphe nuclei, followed consecutively by the striatum, hippocampal complex, cingulate cortex, neocortex, and cerebellum. The time–activity curve for the fraction of unchanged 11C-MADAM in plasma was best described by a sigmoid function. After 50 min, the fraction was 40%. The labeled metabolites were more polar than the mother compound. The compartment model approaches converged, and could describe the time–activity curves in all regions. The total volume of distribution (Vt) was similar to the regional distribution volumes obtained by the linear graphic analysis. The binding potentials (BPs) for 6 different approaches yielded similar values in all regions but the raphe nuclei, where the 2 equilibrium methods provided lower values. Conclusion: The regional binding distribution of 11C-MADAM is consistent with postmortem data acquired with 3H-MADAM as well as with that of other reference ligands in vitro. The time–activity curves were well described by current major quantitative approaches. The suitability of the cerebellum as a reference region for nonspecific 11C-MADAM binding could be confirmed, thus paving the way for experimentally less demanding approaches, such as the simplified reference tissue model, for applied clinical studies.

【 授权许可】

Unknown