Radiosynthesis and biological evaluation of alpha-[F-18]fluoromethyl phenylalanine for brain tumor imaging.

Academic Article


  • OBJECTIVES: Radiolabeled amino acids have proven utility for imaging brain tumors in humans, particularly those that target system L amino acid transport. We have prepared the novel phenylalanine analogue, (FMePhe, 9), as part of an effort to develop new system L tracers that can be prepared in high radiochemical yield through nucleophilic [(18)F]fluorination. The tumor imaging properties of both enantiomers of this new tracer were evaluated through cell uptake, biodistribution and microPET studies in the mouse DBT model of high grade glioma. METHODS: The non-radioactive form of 9 and the cyclic sulfamidate labeling precursor were prepared from commercially available racemic α-benzylserine. Racemic [(18)F]9 was prepared from the labeling precursor in two steps using standard[(18)F]fluoride nucleophilic reaction conditions followed by acidic deprotection. The individual enantiomers [(18)F]9a and [(18)F]9b were isolated using preparative chiral HPLC. In vitro uptake inhibition assays were performed with each enantiomer using DBT cells. Biodistribution and microPET/CT studies were performed with each enantiomer in male BALB/c mice at approximately 2 weeks after implantation of DBT tumor cells. RESULTS: Radiolabeling of the cyclic sulfamidate precursor 5 provides racemic [(18)F]9 in high radiochemical yield (60%-70%, n=4) and high radiochemical purity (>96%, n=4). In vitro uptake assays demonstrate that both [(18)F]9a and [(18)F]9b undergo tumor cell uptake through system L transport. The biodistribution studies using the single enantiomers [(18)F]9a and [(18)F]9b demonstrated good tumor uptake with lower uptake in most normal tissues, and [(18)F]9a had higher tumor uptake than [(18)F]9b. MicroPET imaging demonstrated good tumor visualization within 10 min of injection, rapid uptake of radioactivity, and tumor to brain ratios of approximately 6:1 at 60 min postinjection. CONCLUSIONS: The novel PET tracer, [(18)F]FMePhe, is readily synthesized in good yield from a cyclic sulfamidate precursor. Biodistribution and microPET studies in the DBT model demonstrate good tumor to tissue ratios and tumor visualization, with enantiomer [(18)F]9a having higher tumor uptake. However, the brain availability of both enantiomers was lower than expected for system L substrates, suggesting the [(18)F]fluorine group in the β-position affects uptake of these compounds by system L transporters.
  • Published In


  • Animals, Biological Transport, Brain Neoplasms, Glioma, Male, Mice, Multimodal Imaging, Neoplasm Grading, Phenylalanine, Radiochemistry, Radionuclide Imaging
  • Digital Object Identifier (doi)

    Author List

  • Huang C; Yuan L; Rich KM; McConathy J
  • Start Page

  • 498
  • End Page

  • 506
  • Volume

  • 40
  • Issue

  • 4