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

Chaofeng Huang, Liya Yuan, Keith M. Rich, Jonathan McConathy

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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, α-[18F]fluoromethyl phenylalanine (FMePhe, 9), as part of an effort to develop new system L tracers that can be prepared in high radiochemical yield through nucleophilic [18F]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 [18F]9 was prepared from the labeling precursor in two steps using standard[18F]fluoride nucleophilic reaction conditions followed by acidic deprotection. The individual enantiomers [18F]9a and [18F]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 2weeks after implantation of DBT tumor cells. Results: Radiolabeling of the cyclic sulfamidate precursor 5 provides racemic [18F]9 in high radiochemical yield (60%-70%, n=4) and high radiochemical purity (>96%, n=4). In vitro uptake assays demonstrate that both [18F]9a and [18F]9b undergo tumor cell uptake through system L transport. The biodistribution studies using the single enantiomers [18F]9a and [18F]9b demonstrated good tumor uptake with lower uptake in most normal tissues, and [18F]9a had higher tumor uptake than [18F]9b. MicroPET imaging demonstrated good tumor visualization within 10min of injection, rapid uptake of radioactivity, and tumor to brain ratios of approximately 6:1 at 60min postinjection. Conclusions: The novel PET tracer, [18F]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 [18F]9a having higher tumor uptake. However, the brain availability of both enantiomers was lower than expected for system L substrates, suggesting the [18F]fluorine group in the β-position affects uptake of these compounds by system L transporters.

Original languageEnglish
Pages (from-to)498-506
Number of pages9
JournalNuclear Medicine and Biology
Volume40
Issue number4
DOIs
StatePublished - May 2013

Keywords

  • Amino acid
  • Fluorine-18
  • Glioma
  • Positron emission tomography
  • System L

Fingerprint

Dive into the research topics of 'Radiosynthesis and biological evaluation of alpha-[F-18]fluoromethyl phenylalanine for brain tumor imaging'. Together they form a unique fingerprint.

Cite this