title: Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Duke University Medical Center, Department of Radiology, Division of Nuclear Medicine, DUMC; Box 3949, Durham, North Carolina 27710. United States.
authors.forename: Bennett B
authors.initials: BB
authors.lastname: Chin
authors.affiliation: Department of Radiology, Duke University Medical Center, Division of Nuclear Medicine, North Carolina 27710. United States.
authors.forename: Darryl
authors.initials: D
authors.lastname: McDougald
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710. United States.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Weitzel
authors.affiliation: Department of Radiology, Duke University Medical Center, Division of Nuclear Medicine, North Carolina 27710. United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hawk
authors.affiliation: Department of Radiology, Duke University Medical Center, Division of Nuclear Medicine, North Carolina 27710, United States.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Reiman
authors.affiliation: Department of Radiology, Duke University Medical Center, Division of Nuclear Medicine, North Carolina 27710, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zalutsky
authors.affiliation: Department of Radiology, Duke University Medical Center, Division of Nuclear Medicine, North Carolina 27710, United States.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Vaidyanathan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007930:Leucine / Q000031:analogs & derivatives* / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D000072078:Positron Emission Tomography Computed Tomography; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D007930:Leucine
keywords: Leucine; amino acid; dosimetry; fluoroleucine; positron emission tomography; tumor imaging