Synthesis and biological evaluation of anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid (anti-2-[18F]FACBC) in rat 9L gliosarcoma

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2140-3. doi: 10.1016/j.bmcl.2010.02.048. Epub 2010 Feb 14.

Abstract

A new [(18)F] labeled amino acid anti-1-amino-2-[(18)F]fluoro-cyclobutyl-1-carboxylic acid 9 (anti-2-[(18)F]FACBC) was synthesized in 30% decay-corrected yield with high radiochemical purity over 99%. The cyclic sulfamidate precursor was very stable and highly reactive towards nucleophilic radiofluorination. Cell uptake assays with rat 9L gliosarcoma cells showed that [(18)F]9 was transported into tumor cells via multiple amino acid transport systems, including L and A systems. Biodistribution study in rats with intracranial 9L gliosarcoma tumors demonstrated that [(18)F]9 had a rapid and prolonged accumulation in tumors with 26:1 tumor to brain ratio at 120 min post-injection. In this model, [(18)F]9 is a potential PET tracer for brain tumor imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / pharmacokinetics
  • Cell Line, Tumor
  • Cell Membrane Permeability
  • Cyclobutanes / chemical synthesis*
  • Cyclobutanes / pharmacokinetics
  • Fluorine Radioisotopes* / chemistry
  • Fluorine Radioisotopes* / pharmacokinetics
  • Gliosarcoma / diagnostic imaging*
  • Male
  • Positron-Emission Tomography / methods*
  • Rats
  • Rats, Inbred F344

Substances

  • Carboxylic Acids
  • Cyclobutanes
  • Fluorine Radioisotopes
  • fluciclovine F-18