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EJNMMI Research
Published in: EJNMMI Research 1/2014

Open Access 01-12-2014 | Original research

Strategy to develop a MAO-A-resistant 5-hydroxy-l-[β-11C]tryptophan isotopologue based on deuterium kinetic isotope effects

Authors: Jonas Eriksson, Ola Åberg, Ram Kumar Selvaraju, Gunnar Antoni, Lars Johansson, Olof Eriksson

Published in: EJNMMI Research | Issue 1/2014

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Abstract

Background

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.

Methods

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.

Results

[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.

Conclusions

Partial deuteration of the β-position yields improved resistance to MAO-A-mediated degradation in vitro but not in vivo.
Appendix
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Metadata
Title
Strategy to develop a MAO-A-resistant 5-hydroxy-l-[β-11C]tryptophan isotopologue based on deuterium kinetic isotope effects
Authors
Jonas Eriksson
Ola Åberg
Ram Kumar Selvaraju
Gunnar Antoni
Lars Johansson
Olof Eriksson
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2014
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-014-0062-2

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