title: Strategy to develop a MAO-A-resistant 5-hydroxy-L-[β-(11)C]tryptophan isotopologue based on deuterium kinetic isotope effects.
abstract: BACKGROUND
  The serotonin precursor 5-hydroxy-L-[β-(11)C]tryptophan ([(11)C]HTP) is in clinical use for localization of neuroendocrine tumors and has been suggested as a proxy marker for pancreatic islet cells. However, degradation by monoamine oxidase-A (MAO-A) reduces retention and the contrast to non-endocrine tissue.
  
  
  METHODS
  A synthesis method was developed for 5-hydroxy-L-[β- (11)C(2)H]tryptophan ([(11)C]DHTP), an isotopologue of [(11)C]HTP, labeled with (11)C and (2)H at the β-position adjacent to the carbon involved in MAO-A decarboxylation. MAO-A-mediated degradation of [(11)C]DHTP was evaluated and compared to non-deuterated [(11)C]HTP.
  
  
  RESULTS
  [(11)C]DHTP was synthesized with a radiochemical purity of >98%, radioactivity of 620 ± 190 MBq, and deuterium ((2)H or (2)H2) incorporation at the β-position of 22% ±5%. Retention and resistance to MAO-A-mediated degradation of [(11)C]DHTP were increased in cells but not in non-human primate pancreas.
  
  
  CONCLUSIONS
  Partial deuteration of the β-position yields improved resistance to MAO-A-mediated degradation in vitro but not in vivo.
authors.affiliation: Preclinical PET Platform (PPP), Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, SE-751 83, Uppsala, Sweden, Jonas.p.eriksson@akademiska.se.
authors.forename: Jonas
authors.initials: J
authors.lastname: Eriksson
authors.forename: Ola
authors.initials: O
authors.lastname: Åberg
authors.forename: Ram Kumar
authors.initials: RK
authors.lastname: Selvaraju
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
authors.forename: Lars
authors.initials: L
authors.lastname: Johansson
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson