Quincoces, G; Collantes, M; Catalan, R; Ecay, M; Prieto, E; Martino, E; ... Penuelas, I; + view all Quincoces, G; Collantes, M; Catalan, R; Ecay, M; Prieto, E; Martino, E; Blesa, FJ; Alvarez-Erviti, L; Areses, P; Arbizu, J; Obeso, JA; Marti-Climent, JM; Richter, JA; Penuelas, I; - view fewer (2008) Quick and simple synthesis of C-11-(+)-alpha-dihydrotetrabenazine to be used as a pet radioligand of vesicular monoamine transporters. REV ESP MED NUCL , 27 (1) 13 - 21.
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Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9,10-dimethoxy-1,3,4,6,7-hexahydro-11bH-benzo[a]-quinolizine, DTBZ) has become the ideal radioligand for the presynaptic vesicular monoamine transporter VMAT2 based on its high binding affinity and optimal lipophilicity. Objective. To develop an automatic procedure for labelling DTBZ with carbon-11, which has been shown to be a highly effective marker for in vivo studies of neuronal losses in animal models with Parkinson's disease using positron emission tomography (PET).Materials and methods. We have developed a new fully automated synthesis procedure to obtain C-11-(+)DTBZ quickly and simply through labelling the precursor -(+)desmethyldihydrotetrabenazine- at room temperature in the presence of dimethyl sulfoxide (DMSO) and potassium hydroxide (KOH), using (CH3I)-C-11 as primary precursor. The final purification was carried out by solid phase extraction using commercially available cartridges and the residual solvents (DMSO and ethyl ether) were eliminated by evaporation.Results. The whole procedure was automated, and after 54 syntheses, an average production of 1.94 GBq of sterile, pyrogen-free C-11-(+)DTBZ with a radiochemical purity > 99% was obtained with 5 minutes irradiation and 6 minutes of synthesis after (CH3I)-C-11 production. C-11-(+)DTBZ binding to presynaptic dopamine nerve terminals has been demonstrated by MicroPET studies in Wistar rats and M. Fascicularis monkeys.Conclusions. This new synthesis procedure is quick and simple, due to optimised techniques, which have allowed elimination of residual solvents based on their polarity for the final purification. It is also applicable to other automatic syntheses for obtaining compounds labelled by methylation reactions.
|Title:||Quick and simple synthesis of C-11-(+)-alpha-dihydrotetrabenazine to be used as a pet radioligand of vesicular monoamine transporters|
|Keywords:||C-11-(+)dihydrotetrabenazine, monoamine transporters VMAT2, positron emission tomography, synthesis, PARKINSONS-DISEASE, TETRABENAZINE-BINDING, DOPAMINE TRANSPORTER, C-11 TETRABENAZINE, MOUSE-BRAIN, VESICLES, INVIVO, SITE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Clinical Neuroscience|
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