Strategy to develop a MAO-A-resistant 5-hydroxy-L-[beta-C-11]tryptophan isotopologue based on deuterium kinetic isotope effects
2014 (English)In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 4, no 1, 62Article in journal (Refereed) Published
The serotonin precursor 5-hydroxy-L-[β-11C]tryptophan ([11C]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.
A synthesis method was developed for 5-hydroxy-L-[β-11C2H]tryptophan ([11C]DHTP), an isotopologue of [11C]HTP, labeled with 11C and 2H at the β-position adjacent to the carbon involved in MAO-A decarboxylation. MAO-A-mediated degradation of [11C]DHTP was evaluated and compared to non-deuterated [11C]HTP.
[11C]DHTP was synthesized with a radiochemical purity of >98%, radioactivity of 620 ± 190 MBq, and deuterium (2H or 2H2) incorporation at the β-position of 22% ±5%. Retention and resistance to MAO-A-mediated degradation of [11C]DHTP were increased in cells but not in non-human primate pancreas.
Partial deuteration of the β-position yields improved resistance to MAO-A-mediated degradation in vitro but not in vivo.
Place, publisher, year, edition, pages
2014. Vol. 4, no 1, 62
Medicinal Chemistry Radiology, Nuclear Medicine and Medical Imaging
IdentifiersURN: urn:nbn:se:uu:diva-237937DOI: 10.1186/s13550-014-0062-2ISI: 000358052300001OAI: oai:DiVA.org:uu-237937DiVA: diva2:769424