title: Biodistribution and human dosimetry of enantiomer-1 of the synthetic leucine analog anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid.
abstract: BACKGROUND
  The enantiomerically enriched (ee=90%, enantiomer 1) synthetic amino acid (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (anti-2-[(18)F]FACPC-1) accumulates in malignant cells by elevated transport through the sodium-independent system-L (leucine preferring) amino acid transporter. The purpose of this study was to evaluate in vivo uptake and single-dose toxicity of anti-2-[(18)F]FACPC-1 in animals as well as the individual organ and whole-body dose in humans.
  
  
  METHODS
  A DU145 xenograft rodent model was used to measure anti-2-[(18)F]FACPC-1 uptake at 15, 30 and 60 min post-injection. Animals were sacrificed and organs harvested to measure the percent injected activity per organ and to calculate residence time. Anti-2-[(18)F]FACPC-1 toxicity was assessed using a single microdose (37-74 MBq/kg) in nonhuman primates. Their vital signs were monitored for 2 h post-injection for drug-related effects. Human biodistribution studies were collected by sequential whole-body PET/CT scans on six healthy volunteers (three male and three female) for 120 min following a single 247±61 MBq bolus injection of anti-2-[(18)F]FACPC-1. Estimates of radiation dose from anti-2-[(18)F]FACPC-1 to the human body were calculated using recommendations of the MIRD committee and MIRDOSE 3.0 software.
  
  
  RESULTS
  High anti-2-[(18)F]FACPC-1 residence time was observed in the pancreas of the rodent model compared to the human data. No abnormal treatment-related observations were made in the nonhuman primate toxicity studies. Human venous blood showed no metabolites of anti-2-[(18)F]FACPC-1 in the first 60 min post-injection. All volunteers showed initially high uptake in the kidneys followed by a rapid washout phase. The estimated effective dose equivalent was 0.0196 mSv/MBq.
  
  
  CONCLUSIONS
  Anti-2-[(18)F]FACPC-1 showed low background uptake in the brain, thoracic and abdominal cavities of humans, suggesting a possible use for detecting malignant tissues in these regions.
authors: Department of Radiology and Imaging Sciences, Center for Systems Imaging, Emory University, Atlanta, GA 30329, USA. jnye@emory.edu
authors: Jonathon A
authors: JA
authors: Nye
authors: Nashwa
authors: N
authors: Jarkas
authors: David M
authors: DM
authors: Schuster
authors: Bital
authors: B
authors: Savir-Baruch
authors: Ronald J
authors: RJ
authors: Voll
authors: Vernon M
authors: VM
authors: Camp
authors: Mark M
authors: MM
authors: Goodman
mesh_terms: D000328:Adult; D000818:Animals; D001692:Biological Transport; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D011874:Radiometry; D013237:Stereoisomerism
chemical_list: C552703:1-amino-2-fluorocyclopentyl-1-carboxylic acid; D003515:Cycloleucine; D007930:Leucine