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Comparison of (+)-¹¹C-McN5652 and ¹¹C-DASB as Serotonin Transporter Radioligands Under Various Experimental Conditions

¹ Division of Nuclear Medicine, Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland
² Department of Psychiatry and Behavioral Science, The Johns Hopkins School of Medicine, Baltimore, Maryland
³ Vivian Rakoff PET Center, Center for Addiction and Mental Health, The University of Toronto, Toronto, Ontario, Canada
⁴ Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, Maryland

View larger version (77K): [in a new window]   FIGURE 1. Registered PET 11C-DASB and MR images of control baboon brain with superimposed ROIs used for derivation of time–activity curves. PO = pons; CE = cerebellum; TE = temporal cortex; MD = midbrain; HY = hypothalamus; OC = occipital cortex; CA = head of caudate; PU = putamen; TH = thalamus; FR = frontal cortex; PA = parietal cortex; CI = cingulate gyrus.

View larger version (112K): [in a new window]   FIGURE 2. Time–activity curves obtained with (+)-11C-McN5652 (left) and 11C-DASB (right) in various ROIs. Shown are results under baseline conditions and after MDMA treatment and paroxetine pretreatment. Data are expressed in units of nCi/mL/mCi (37 Bq/mL/37 MBq) ID. Measured data are displayed with circles; curves fitted on basis of 3-parameter, 1-tissue compartment model are displayed with lines. Both radioligands show decreased binding in MDMA-treated animal compared with control animal. With both radioligands, paroxetine increased amount of radioactivity reaching brain, measured as time integral of unmetabolized radioligand concentration in arterial plasma. (Continued on page 684.)

View larger version (20K): [in a new window]   FIGURE 3. Effect of prior lesioning of brain 5-HT neurons with MDMA on regional brain 5-HT (A), 5-HIAA (B), and SERT (C) concentrations. FC = frontal cortex; PC = parietal cortex; TC = temporal cortex; OC = occipital cortex; CC = cingulate cortex; Put = putamen; Cd = caudate; Hyp = hypothalamus; Th = thalamus; Cb = cerebellum; DPM = disintegrations per minute.

View larger version (80K): [in a new window]   FIGURE 4. Autoradiography of SERT in baboon brain: coronal section of frontal/temporal/parietal cortex and basal ganglia. In control animal, intense ligand binding is seen in basal ganglia (CD = caudate; PT = putamen). Less binding is seen in temporal cortex (TC), cingulate gyrus (CG), and frontal cortex (FC). MDMA treatment reduced ligand binding in most represented brain structures.

View larger version (55K): [in a new window]   FIGURE 5. Autoradiography of SERT in baboon brain: sagittal section at level of cerebellum and brain stem. In control animal (top), there is high radioligand binding in dorsal brain stem. Less intense, but still significant, binding is seen in ventral and rostral brain stem. There is low but obvious binding in folia cerebelli. In MDMA-treated animal (bottom), binding is decreased in most of these areas, although small islands of high activity remain in dorsal brain stem. In MDMA-treated baboon, radioligand binding is almost completely absent in cerebellum. ROSTRAL and CAUDAL = axes of brain stem; Cb = cerebellum; IC = inferior colliculus; P = pons.