Quick and simple synthesis of ¹¹C-(+)-¦Á-dihydrotetrabenazine to be used as a PET radioligand of vesicular monoamine transporters

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• 作者：G. Quincoces ; ^{gquinfer@unav.es} ; M. Collantes ; R. Catalá ; n ; M. Ecay ; E. Prieto ; E. Martino ; F.J. Blesa ; L. Á ; lvarez-Erviti ; P. Areses ; J. Arbizu ; J.Á ; . Obeso ; J.M. Martí ; -Climent ; J.Á ; . Richter ; I. Peñ ; uelas
• 关键词：11C-(+)dihydrotetrabenazine ; monoamine transporters VMAT2 ; positron emission tomography ; synthesis
• 刊名：Revista Espa?ola de Medicina Nuclear (English Edition)
• 出版年：2008
• 出版时间：January-February 2008
• 年：2008
• 卷：27
• 期：1
• 页码：13-21
• 全文大小：358 K

文摘

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 vivostudies 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 ¹¹C-(+)DTBZ quickly and simply through labelling the precursor ?+)desmethyldihydrotetrabenazine?at room temperature in the presence of dimethyl sulfoxide (DMSO) and potassium hydroxide (KOH), using ¹¹CH₃I 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 ¹¹C-(+)DTBZ with a radiochemical purity > 99 % was obtained with 5 minutes irradiation and 6 minutes of synthesis after ¹¹CH₃I production. ¹¹C-(+)DTBZ binding to presynaptic dopamine nerve terminals has been demonstrated by MicroPET studies in Wistar rats and M. Fascicularismonkeys.

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.