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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

In vitro and in vivo characterisation of nor-beta-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain.

Radiolabelled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2beta-Carbomethoxy-3beta-(4-iodophenyl)nortropane (nor-beta-CIT) is a des-methyl analogue of beta-CIT, which in vitro has tenfold higher affinity (IC50=0.36 nM) to the serotonin transporter than beta-CIT (IC50=4.2 nM). Nor-beta-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-beta-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [125I]nor-beta-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 microM) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [11C]nor-beta-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [11C]nor-beta-CIT were 20%-40% higher than those previously obtained with [11C]beta-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-beta-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain.[1]


  1. In vitro and in vivo characterisation of nor-beta-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain. Bergström, K.A., Halldin, C., Hall, H., Lundkvist, C., Ginovart, N., Swahn, C.G., Farde, L. European journal of nuclear medicine. (1997) [Pubmed]
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