11C-Fallypride: radiosynthesis and preliminary evaluation of a novel dopamine D2/D3 receptor PET radiotracer in non-human primate brain

Bioorg Med Chem. 2004 Jan 2;12(1):95-102. doi: 10.1016/j.bmc.2003.10.020.

Abstract

Fallypride [benzamide, 5-(3-fluoropropyl)-2,3-dimethoxy-N-[(2S)-1-(2-propenyl)-2-pyrrolidinyl]methyl]-, CAS RN 166173-78-0] is a selective dopamine D2/D3 receptor antagonist. Carbon-11 labeled fallypride may serve as a radiotracer for use in biomedical imaging technique positron emission tomography (PET). The precursor, 5-(3-fluoropropyl)-2-hydroxy-3-methoxy-N-[(2S)-1-(2-propenyl)-2-pyrrolidinyl]methyl]benzamide was synthesized from 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid, methyl ester in seven steps with approximately 10% overall chemical yield. Using this precursor (11)C-fallypride was produced by radiolabeling with (11)C-methyl iodide in 25-40% radiochemical yields with specific activities of 200-1000 Ci/mmol. PET imaging studies in nonhuman primates with (11)C-fallypride showed radiotracer localization in dopaminergic brain regions such as caudate, putamen, thalamus and cortex. This regional localization of (11)C-fallypride is similar to that observed previously for (18)F-fallypride. The results suggest (11)C-fallypride is a useful PET radiotracer for imaging dopamine D2/D3 receptors.

Publication types

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

MeSH terms

  • Animals
  • Benzamides / metabolism*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbon Radioisotopes / metabolism
  • Dopamine Antagonists / chemistry
  • Dopamine Antagonists / metabolism*
  • Dopamine D2 Receptor Antagonists
  • Drug Evaluation, Preclinical / methods
  • Macaca mulatta
  • Pyrrolidines / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3
  • Tomography, Emission-Computed / methods*

Substances

  • Benzamides
  • Carbon Radioisotopes
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3