Synthesis of 3beta-(4-[18F]fluoromethylphenyl)- and 3beta-(2-[18F] fluoromethylphenyl)tropane-2beta-carboxylic acid methyl esters: new ligands for mapping brain dopamine transporter with positron emission tomography

Nucl Med Biol. 1999 Jul;26(5):529-35. doi: 10.1016/s0969-8051(99)00023-2.

Abstract

The synthesis of two new dopamine transporter ligands, 3beta-(4-fluoromethylphenyl)tropane-2beta-carboxylic acid methyl ester and 3beta-(2-fluoromethylphenyl)tropane-2beta-carboxylic acid methyl ester, and their spectral characterization are described. The precursors for these ligands were prepared by TiCl4 catalyzed chloromethylation of 3beta-phenyltropane-2beta-carboxylic acid methyl ester followed by separation of the isomeric product mixture of 2- and 4-chloromethylphenyltropane derivatives. Reaction of the chloromethyl analogs with no-carrier-added [18F]fluoride ion followed by high performance liquid chromatography purification provided the corresponding [18F]fluoromethyltropanes, in good radiochemical yields, useful for imaging the brain dopamine transporter system in vivo with positron emission tomography.

Publication types

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

MeSH terms

  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism*
  • Cocaine / analogs & derivatives*
  • Cocaine / chemical synthesis
  • Cocaine / pharmacokinetics
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorine Radioisotopes / pharmacokinetics*
  • Humans
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Molecular Conformation
  • Molecular Structure
  • Nerve Tissue Proteins*
  • Tomography, Emission-Computed / methods

Substances

  • 3beta-(2-fluoromethylphenyl)tropane-2beta-carboxylic acid methyl ester
  • 3beta-(4-fluoromethylphenyl)tropane-2beta-carboxylic acid methyl ester
  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Cocaine
  • Dopamine