Fluorine-18-labelled NCQ 115, a selective dopamine D-2 receptor ligand. Preparation and positron emission tomography

Nucl Med Biol. 1994 May;21(4):627-31. doi: 10.1016/0969-8051(94)90028-0.

Abstract

NCQ 115 ((+)-(R)-5-bromo-N-((1-(4-fluorobenzyl)-2-pyrrolidinyl)methyl)-2, 3-dimethoxybenzamide) is a selective dopamine D-2 receptor antagonist. NCQ 115 has a fluorine in a synthetically suitable position in the parent compound and was therefore suggested as a potential 18F-labelled radioligand for positron emission tomography (PET). [18F]4-Fluorobenzyl iodide was prepared in a 3-step synthesis from [18F]fluoride. N-4-Fluorobenzylation of the corresponding secondary pyrrolidine precursor was performed in DMF followed by purification with semi-preparative HPLC. The total radiochemical yield (EOB and decay-corrected) was 15-20% with a total synthesis time of 90 min and a radiochemical purity > 99%. The specific radioactivity at the end of synthesis (EOS) was about 1500 Ci/mmol (55.5 GBq/mumol). [18F]NCQ 115 was injected into a Cynomolgus monkey for PET examination of brain in vivo. There was a conspicuous uptake of radioactivity in the monkey striatum. A specific [18F]NCQ 115 binding reached a peak after about 60 min which indicates equilibrium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacokinetics
  • Brain / metabolism
  • Dopamine Antagonists / chemical synthesis*
  • Dopamine Antagonists / pharmacokinetics
  • Dopamine D2 Receptor Antagonists
  • Fluorine Radioisotopes* / chemistry
  • Isotope Labeling / methods
  • Ligands
  • Macaca fascicularis
  • Male
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacokinetics
  • Receptors, Dopamine D2 / metabolism*
  • Tomography, Emission-Computed

Substances

  • Benzamides
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Fluorine Radioisotopes
  • Ligands
  • Pyrrolidines
  • Receptors, Dopamine D2
  • 5-bromo-2,3-dimethoxy-N-((1-(4-fluorobenzyl)-2-pyrrolidinyl)methyl)benzamide