[O-methyl-11C]beta-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: preparation, autoradiography, metabolite studies, and positron emission tomography examinations

Nucl Med Biol. 1995 Oct;22(7):905-13. doi: 10.1016/0969-8051(95)00029-w.

Abstract

beta-CIT-FP [N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane] is a cocaine analogue with a high affinity for the dopamine transporter. [O-methyl-11C]beta-CIT-FP ([11C]beta-CIT-FP) was prepared by O-alkylation of the free acid with [11C]methyl iodide. The total radiochemical yield of [11C]beta-CIT-FP was 50 to 60% with an overall synthesis time of 30 min. The radiochemical purity was > 99%, and the specific radioactivity at time of injection was about 37 GBq/mumol (1000 Ci/mmol). Autoradiographic examination of [11C]beta-CIT-FP binding in human brain postmortem demonstrated specific binding in the caudate nucleus and putamen. Positron emission tomography (PET) examination of [11C]beta-CIT-FP in a Cynomolgus monkey demonstrated accumulation in the striatum with a striatum-to-cerebellum ratio of about 8 after 60 min. Equilibrium in the striatum was attained within 70 to 90 min. The radioactivity ratios of thalamus/cerebellum and neocortex/cerebellum were about 2 and 1.5, respectively. In a displacement experiment, radioactivity in the striatum but not in the cerebellum was reduced after injection of beta-CIT, indicating that striatal radioactivity following injection of [11C]beta-CIT-FP is associated with dopamine transporter sites and that the binding is reversible. The fraction of the total radioactivity in plasma representing [11C]beta-CIT-FP determined by high-performance liquid chromatography (HPLC) was 84% at 15 min and 50% at 95 min. [11C]beta-CIT-FP should be a useful PET radioligand for the quantitation of dopamine transporters in the human brain in vivo.

Publication types

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

MeSH terms

  • Animals
  • Autoradiography
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Carbon Radioisotopes*
  • Carrier Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Dopamine Plasma Membrane Transport Proteins
  • Humans
  • Hydrocarbons, Iodinated / chemistry
  • Macaca fascicularis
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Radioligand Assay
  • Tomography, Emission-Computed / methods
  • Tropanes / blood
  • Tropanes / chemistry
  • Tropanes / metabolism

Substances

  • Carbon Radioisotopes
  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Hydrocarbons, Iodinated
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
  • methyl iodide