Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine

Curr Radiopharm. 2017;10(1):41-50. doi: 10.2174/1874471009666161230114954.


Background: Amino acid transporters, such as LAT1, are overexpressed in aggressive prostate and breast carcinomas, directly influencing pathways of growth and proliferation.

Objective: The purpose of this study was to synthesize and characterize a novel 18F labeled leucine analog, 5-[18F]fluoroleucine, as a potential imaging agent for aggressive tumors which may not be amenable to imaging by FDG PET.

Methods: 5-fluoroleucine was synthesized and characterized, and its 18F-labeled analog was synthesized from a mesylate precursor. First, breast cancer cell line assays were performed to evaluate uptake of 3H- or 14C-labeled L-leucine and other essential amino acids. Both L-leucine and 5- [18F]fluoroleucine were tested for uptake and accumulation over time, and for uptake via LAT1. Biodistribution studies were performed to estimate radiation dosimetry for human studies. Small animal PET / CT studies of a breast cancer were performed to evaluate in vivo 5-[18F]fluoroleucine tumor uptake.

Results: Breast cancer cell lines showed increasing high net accumulation of L-[14C]leucine. Both L-leucine and 5-[18F]fluoroleucine showed increasing uptake over time in in vitro tumor cell assays, and uptake was also shown to occur via LAT1. The biodistribution study of 5-[18F]fluoroleucine showed rapid renal excretion, no significant in vivo metabolism, and acceptable dosimetry for use in humans. In vivo small animal PET / CT imaging of a breast cancer xenograft showed uptake of 5- [18F]fluoroleucine in the tumor, which progressively increased over time.

Conclusion: 5-[18F]fluoroleucine is a leucine analog which may be useful in identifying tumors with high or upregulated expression of amino acid transporters, providing additional information that may not be provided by FDG PET.

Keywords: Leucine; amino acid; dosimetry; fluoroleucine; positron emission tomography; tumor imaging.

MeSH terms

  • Animals
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / radiotherapy*
  • Cell Line, Tumor
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / pharmacology*
  • Humans
  • Image Processing, Computer-Assisted
  • Leucine / analogs & derivatives*
  • Leucine / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Positron Emission Tomography Computed Tomography
  • Radiometry
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacology*
  • Sensitivity and Specificity
  • Tissue Distribution


  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Leucine