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

被引：2
作者：
Eriksson J. [1 ,2 ]
Åberg O. [1 ]
Selvaraju R.K. [1 ]
Antoni G. [1 ,2 ,3 ]
Johansson L. [3 ,4 ]
Eriksson O. [1 ]
机构：
[1] Preclinical PET Platform (PPP), Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, Uppsala
[2] PET Centre, Uppsala University Hospital, Uppsala
[3] Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala University Hospital, Uppsala
[4] AstraZeneca R&D, Pepparedsleden 1, Mölndal
来源：
EJNMMI Research | / 4卷 / 1期
关键词：
5-Hydroxy-tryptophan; Beta cell imaging; Deuterium; Kinetic isotope effect; Neuroendocrine tumors; [!sup]11[!/sup]C]HTP;
D O I：
10.1186/s13550-014-0062-2
中图分类号：
学科分类号：
摘要：
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. © 2014, Eriksson et al.; licensee Springer.
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