[11C]metaraminol, a false neurotransmitter: preparation, metabolite studies and positron emission tomography examination in monkey

Nucl Med Biol. 1996 Apr;23(3):221-7. doi: 10.1016/0969-8051(95)02050-0.

Abstract

No-carrier-added racemic [11C]metaraminol was prepared by a selective condensation of [11C]nitroethane with 3-hydroxy-benzaldehyde using tetrabutylammonium fluoride in tetrahydrofuran (THF) as a catalyst, followed by a reduction with Raney nickel in formic acid. [11C]Metaraminol was produced in 30 to 45% decay-corrected yield from [11C]nitroethane (13 to 20% decay corrected from [11C]CO2) within 45 to 55 min total synthesis time. Reversed phase high-performance liquid chromatography (HPLC) was used for the separation of the racemic erythro- and threo-forms of [11C]metaraminol. The radiochemical purity was higher than 98%, and the specific radioactivity at the end of synthesis was 500 to 800 Ci/mmol (18 to 30 GBq/mumol). Positron emission tomography (PET) examination of racemic erythro-[11C]metaraminol in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. Following pretreatment with the selective norepinephrine reuptake inhibitor desipramine, the radioactivity uptake in the myocardium was markedly reduced (80%), demonstrating the specificity of erythro-[11C]metaraminol for the norepinephrine reuptake system of the heart. Pretreatment with desipramine had no effect on radioactivity in lung. The metabolism was rapid for [11C]metaraminol. The amounts of the total radioactivity representing [11C]metaraminol in plasma, determined by HPLC, were 14% at 6 min and 8% at 34 min. The high specific uptake of racemic erythro-[11C]metaraminol indicates that enantiomerically pure (R,S)-[11C]metaraminol has potential for detailed mapping of the sympathetic innervation of the human myocardium.

Publication types

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

MeSH terms

  • Animals
  • Carbon Dioxide
  • Carbon Radioisotopes*
  • Desipramine / pharmacology
  • Ethane / analogs & derivatives
  • Heart / diagnostic imaging
  • Heart / drug effects
  • Humans
  • Indicators and Reagents
  • Isomerism
  • Isotope Labeling / methods
  • Macaca fascicularis
  • Male
  • Metaraminol / chemical synthesis
  • Metaraminol / pharmacokinetics*
  • Myocardium / metabolism*
  • Nitroparaffins
  • Norepinephrine / pharmacology
  • Tissue Distribution
  • Tomography, Emission-Computed / methods*

Substances

  • Carbon Radioisotopes
  • Indicators and Reagents
  • Nitroparaffins
  • Carbon Dioxide
  • nitroethane
  • Metaraminol
  • Ethane
  • Desipramine
  • Norepinephrine