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.