title: 5-Fluoro-[β-¹¹C]-L-tryptophan is a functional analogue of 5-hydroxy-[β-¹¹C]-L-tryptophan in vitro but not in vivo.
abstract: BACKGROUND
  5-Hydroxy-[β-(11)C]-L-tryptophan ([(11)C]HTP) is an established positron emission tomography (PET) imaging agent for neuroendocrine tumors (NETs). It has also been used for other clinical research purposes in neurology and diabetes. However, its widespread use is limited by the short physical half-life of the radionuclide and a difficult radiosynthesis. Therefore, a Fluorine-18 labeled analogue, 5-[(18)F]Fluoro-L-tryptophan ([(18)F]FTRP), has been proposed as a functional analogue. There is no published method for the synthesis of L-[(18)F]FTRP. We have therefore developed a synthesis of 5-fluoro-[β-(11)C]-L-tryptophan ([(11)C]FTRP), based on the existing chemo-enzymatic method for [(11)C]HTP and evaluated the potential usefulness of radiolabeled FTRP as a substitute for [(11)C]HTP.
  
  
  METHODS
  The in vitro and in vivo behavior of [(11)C]FTRP, including the dependence of key enzymes in the serotonergic metabolic pathway, was investigated in NET cell lines, NET xenograft carrying immunodeficient mice, normal rats and in non-human primate. [(11)C]HTP was used for direct comparison.
  
  
  RESULTS
  Uptake of [(11)C]FTRP in NET cell lines in vitro was mediated by enzymes involved in serotonin synthesis and metabolism, similar to [(11)C]HTP. In vivo biodistribution, either in rodent or non-human primate, was not affected by selectively inhibiting enzymatic steps in the serotonergic metabolic pathway.
  
  
  CONCLUSIONS
  [(11)C]FTRP has in vitro biological function similar to that of [(11)C]HTP. However, this function is not retained in vivo as shown by biodistribution and PET/CT studies. Radiolabeled FTRP is thus not likely to provide an advantage over [(11)C]HTP in PET imaging in oncology, neurology or diabetes.
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala, Sweden. olof.eriksson@pet.medchem.uu.se
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Selvaraju
authors.forename: Beatrice
authors.initials: B
authors.lastname: Borg
authors.forename: Veronika
authors.initials: V
authors.lastname: Asplund
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
mesh_terms: D000818:Animals; D018278:Carcinoma, Neuroendocrine / Q000000981:diagnostic imaging / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D007515:Islets of Langerhans / Q000000981:diagnostic imaging; D008252:Macaca fascicularis; D051379:Mice; D049268:Positron-Emission Tomography; D011854:Radiochemistry; D051381:Rats; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: C518855:5-hydroxy-L-(beta-11C)tryptophan; C026927:5-fluorotryptophan; D014364:Tryptophan