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Preparation of a potential positron emission tomographic radioligand for the dopamine transporter

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Abstract

NNC 12-0722 (1-[2-(bis(4-fluorophenyl)methoxy)ethyl]-4-methyl piperazine) is a new selective inhibitor of the dopamine transporter. [11C]NNC 12-0722 was prepared by N-methylation of the desmethyl compound with [11C]methyl iodide. The total radiochemical yield of [11C]NNC 12-0722 was 40%–50% with an overall synthesis time of 30–35 min. The radiochemical purity was higher than 99% and the specific radioactivity about 1500 Ci/mmol (55 GBq/μmol). Autoradiographic examination of [11C]NNC 12-0722 binding on whole hemisphere cryosections from human brain post mortem demonstrated specific binding in the caudate nucleus and putamen. In a positron emission tomographic examination of [11C]NNC 12-0722 in a cynomolgus monkey there was a rapid uptake of radioactivity in the brain. In the striatum, a region with a high density of dopamine transporters, the radioactivity was two times higher than in the cerebellum. These results indicate that [11C]NNC 12-0722 may be a useful radioligand for labelling of the dopamine transporter in man.

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Authors and Affiliations

  1. Karolinska Institutet, Department of Psychiatry and Psychology, Karolinska Hospital, S-17176, Stockholm, Sweden

    Lars Müller, Christer Halldin, Christian Foged, Per Karlsson, Håkan Hall, Carl-Gunnar Swahn & Lars Farde

  2. Novo Nordisk A/S, Pharmaceuticals Division, DK-2760, Målöv, Denmark

    Lars Müller, Christian Foged, Peter D. Suzdak, Rolf Hohlweg & Erik B. Nielsen

Authors
  1. Lars Müller
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  2. Christer Halldin
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  3. Christian Foged
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  4. Per Karlsson
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  5. Håkan Hall
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  6. Carl-Gunnar Swahn
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  7. Peter D. Suzdak
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  8. Rolf Hohlweg
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  9. Erik B. Nielsen
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  10. Lars Farde
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Correspondence to: C. Halldin

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Müller, L., Halldin, C., Foged, C. et al. Preparation of a potential positron emission tomographic radioligand for the dopamine transporter. Eur J Nucl Med 21, 131–137 (1994). https://doi.org/10.1007/BF00175760

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  • DOI: https://doi.org/10.1007/BF00175760

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