Fluorine-18-FPCT: a PET radiotracer for imaging dopamine transporters

J Nucl Med. 1997 Jan;38(1):119-26.

Abstract

Fluorine-18-labeled 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane (FPCT) has been synthesized as a new dopamine transporter imaging agent.

Methods: Fluorine-18 was introduced into 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane by preparation of 1-[18F]fluoro-3-iodopropane followed by alkylation of 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)nortropane.

Results: Tissue distribution studies in rats with [18F]FPCT showed high striatal uptake (0.70% dose/g at 60 min; 0.38% dose/g at 120 min) and good striatal-to-cerebellum ratios (5.5 at 60 min; 6.2 at 120 min). Imaging studies in rhesus monkeys (n = 2) with [18F]FPCT showed high uptake and retention in the putamen (P) (P = 0.03%-0.12% dose/g; at 115 min) and good putamen-to-cerebellum ratios of 3.40-3.43 at 115 min. Plasma metabolites were analyzed in rhesus monkeys (n = 2) by ether extraction and HPLC. The radioactivity in the ether-extractable fraction displayed a single peak that corresponded on HPLC to unmetabolized authentic FPCT.

Conclusion: These results suggest that [18F]FPCT is an excellent candidate for PET imaging of dopamine transporters.

Publication types

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

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Carrier Proteins / metabolism*
  • Contrast Media*
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Fluorine Radioisotopes / pharmacokinetics*
  • Macaca mulatta
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins / metabolism*
  • Nortropanes / chemical synthesis
  • Nortropanes / pharmacokinetics*
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Tomography, Emission-Computed*

Substances

  • 2-carbomethoxy-3-(4-chlorophenyl)-8-(3-fluoropropyl)nortropane
  • Carrier Proteins
  • Contrast Media
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Nortropanes
  • Radiopharmaceuticals