Article (Scientific journals)
Fully automated radiosynthesis of N1-[18F]fluoroethyl-tryptophan and study of its biological activity as a new potential substrate for indoleamine 2,3-dioxygenase PET imaging
Henrottin, Jean; Lemaire, Christian; Egrise, Dominique et al.
2016In Nuclear Medicine and Biology, 43 (6), p. 379-389
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Keywords :
Tryptophan; PET imaging; Indoleamine 2,3-dioxygenase; 1-(2-[18F]fluoroethyl)tryptophan; Fully automated radiosynthesis; FASTlab
Abstract :
[en] Introduction: Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial step in the catabolism of L-tryptophan along the kynurenine pathway and exerts immunosuppressive properties in inflammatory and tumor tissues by blocking locally T-lymphocyte proliferation. Recently, 1-(2-[19F]fluoroethyl)-DL-tryptophan (1-[19F]FE-DL-Trp) was reported as a good and specific substrate of this enzyme. Herein, the radiosynthesis of its radioactive isotopomer (1-[18F]FE-DL-Trp, DL-[18F]5) is presented along with in vitro enzymatic and cellular uptake studies. Methods: The one-pot n.c.a. radiosynthesis of this novel potential PET imaging tracer, including HPLC purification and formulation, has been fully automated on a FASTlabTM synthesizer. Chiral separation of both isomers and their formulation were implemented on a second cassette. In vitro enzymatic and cellular uptake studies were then conducted with the D-, L- and DL-radiotracers. Results: The radiolabeling of the tosylate precursor was performed in DMF (in 5 min; RCY: 57% (d.c.), n=3). After hydrolysis, HPLC purification and formulation, DL-[18F]5 was obtained with a global radiochemical yield of 18±3% (not decay corrected, n=7, in 80 min) and a specific activity of 600±180 GBq/µmol (n=5). The subsequent separation of L- and D-enantiomers was performed by chiral HPLC and both were obtained after formulation with a RCY (d.c.) of 6.1% and 5.8%, respectively. In vitro enzymatic assays reveal that L-[18F]5 is a better substrate than D-[18F]5 for human IDO. In vitro cellular assays show an IDO-specific uptake of the racemate varying from 30% to 50% of that of L-[18F]5, and a negligible uptake of D-[18F]5. Conclusion: In vitro studies show that L-[18F]5 is a good and specific substrate of hIDO, while presenting a very low efflux. These results confirm that L-[18F]5 could be a very useful PET radiotracer for IDO expressing cells in cancer imaging.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Chemistry
Author, co-author :
Henrottin, Jean ;  Université de Liège > Centre de recherches du cyclotron
Lemaire, Christian ;  Université de Liège > Centre de recherches du cyclotron
Egrise, Dominique
Zervosen, Astrid 
Van den Eynde, Benoit
Plenevaux, Alain  ;  Université de Liège > Centre de recherches du cyclotron
Franci, Xavier
Goldman, Serge
Luxen, André ;  Université de Liège > Département de chimie (sciences) > Laboratoire de chimie organique de synthèse
Language :
English
Title :
Fully automated radiosynthesis of N1-[18F]fluoroethyl-tryptophan and study of its biological activity as a new potential substrate for indoleamine 2,3-dioxygenase PET imaging
Publication date :
June 2016
Journal title :
Nuclear Medicine and Biology
ISSN :
0969-8051
Publisher :
Pergamon Press, Oxford, United Kingdom
Volume :
43
Issue :
6
Pages :
379-389
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 14 March 2016

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