Home > Publications database > Preparation of 5-[18F],7-difluoro- and 5,7-[18F]difluorotryptophans > print

001     1027698
005     20240625201957.0
024 7 _ |a 10.1016/S0969-8051(22)00110-X
|2 doi
024 7 _ |a 0969-8051
|2 ISSN
024 7 _ |a 1872-9614
|2 ISSN
037 _ _ |a FZJ-2024-04009
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Kolks, Niklas
|0 P:(DE-Juel1)178654
|b 0
|e Corresponding author
|u fzj
111 2 _ |a 24th International Symposium on Radiopharmaceutical Sciences
|g ISRS2022
|c Nantes
|d 2022-05-29 - 2022-06-03
|w France
245 _ _ |a Preparation of 5-[18F],7-difluoro- and 5,7-[18F]difluorotryptophans
260 _ _ |c 2022
336 7 _ |a Conference Paper
|0 33
|2 EndNote
336 7 _ |a Other
|2 DataCite
336 7 _ |a INPROCEEDINGS
|2 BibTeX
336 7 _ |a conferenceObject
|2 DRIVER
336 7 _ |a LECTURE_SPEECH
|2 ORCID
336 7 _ |a Conference Presentation
|b conf
|m conf
|0 PUB:(DE-HGF)6
|s 1719304005_18351
|2 PUB:(DE-HGF)
|x After Call
520 _ _ |a Objective: Tryptophan (Trp) is an essential proteinogenic aminoacid with an indole side chain that can serve as a precursor for differ-ent signaling molecules. The two main branches of Trp metabolism -serotonin/melatonin biosynthesis and the kynurenine pathway - aredifferentially altered in a variety of neurological, psychiatric andoncological diseases. Positron emission tomography (PET) withradiolabeled Trp analogs like 7-[ 18 F]Fluorotryptophan (7-[ 18 F]FTrp),which has been recently introduced and underwent first in-humanstudies, represents a promising approach for in vivo imaging of Trpmetabolism [1]. However, imaging probes capable of selectivelyvisualizing different Trp metabolic pathways are still lacking. Theobjective of this work was the preparation of 5-[ 18 F],7-difluoro- and5,7-[ 18 F]-difluorotryptophans ([ 18 F]1 and [ 18 F]2, respectively). 5-FTrpis known to be a good substrate of tryptophan hydroxylase (TPH), akey enzyme of serotonin/melatonin biosynthesis, which transforms5-FTrp into 5-HOTrp. Similarly, [ 18 F]1 should lose the 18 F-label dueto 5-hydroxylation by TPH and thus enable selective visualization of the kynurenine pathway. In contrast, [ 18 F]2 should target both mainbranches of Trp metabolism.Methods: The Ni-BPB-(S,S)-5-BPin-7-F- and -7-BPin-5-F-Trpprecursors (3, 4) were synthesized from 5-Br-7-F- and 7-Br-5-F-indoles, which were in turn prepared from 4-Br-2-F- and 2-Br-4-F-anilines. Miyaura borylation of these heterocylces furnished5-BPin-7-F- and 7-BPin-5-F-indoles, which were transformedinto N,N,N-(5-Bpin-7-F-indolyl)- and N,N,N-(7-Bpin-5-F-indolyl)-methyltrimethylammonium iodides using a Mannich type reactionfollowed by quaternization with MeI. Finally, alkylation of (S)-Ni-BPB-Gly with the quaternary methylammonium salt afforded the desiredradiolabeling precursors 3 and 4. The latter were 18 F-fluorinatedusing a modified protocol for alcohol-enhanced Cu-mediated radi-ofluorination [2, 3]. Accordingly, [ 18 F]F – was eluted from an anionexchange resin using Et 4 NOTf in MeOH, MeOH was evaporated, and asolution of the respective precursor and copper mediator in nBuOH/DMI (1:2) was added. After stirring of the reaction mixture at 110°Cfor 10 min under air, the radiolabeled intermediates Ni-BPB-(S,S)-5-[ 18 F],7-F 2 Trp ([ 18 F]5) or Ni-BPB-(S,S)-5,7-[ 18 F]-F 2 Trp ([ 18 F]6) were iso-lated by C 18 SPE and decomposed with 2 m HCl at 110°C for 10 min.Finally, HPLC purification and formulation yielded [ 18 F]1 and [ 18 F]2 asready-to-use solutions.Results: The precursors 3 and 4 were synthesized in 13% and 7%yield over 8 steps, respectively. [ 18 F]5 and [ 18 F]6 were prepared inyields of 77% (non-isolated, determined by HPLC). [ 18 F]1 and [ 18 F]2were produced within 68 min in isolated activity yields over twosteps of 35% and 33%, respectively, and in high radiochemical andchemical purities.Conclusion: 5-[ 18 F],7-difluoro- and 5,7-[ 18 F]-difluorotryptophanswere efficiently prepared using alcohol-enhanced Cu-mediatedradiofluorination and can now be subjected to biological evaluationas potential PET-probes for delineation of the main Trp metabolicpathways.Acknowledgements: This work was supported by the GermanResearch Foundation (DFG grants ZL 65/1-1 and ZL 65/3-1).References:[1] B. D. Zlatopolskiy et al.; J. Med. Chem., 2018, 61, 189.[2] A. Craig et al. Chem. Commun., 2020, 56, 9505-9508.[3] J. Zischler et al., Chem. Eur. J. 2017, 23, 3251.
536 _ _ |a 5253 - Neuroimaging (POF4-525)
|0 G:(DE-HGF)POF4-5253
|c POF4-525
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, Journals: juser.fz-juelich.de
700 1 _ |a Zlatopolskiy, Boris
|0 P:(DE-Juel1)185610
|b 1
|u fzj
700 1 _ |a Neumaier, Bernd
|0 P:(DE-Juel1)166419
|b 2
|u fzj
773 _ _ |a 10.1016/S0969-8051(22)00110-X
|0 PERI:(DE-600)1498538-X
|y 2022
|g Vol. 108-109, p. S35 -
|x 0969-8051
856 4 _ |u https://juser.fz-juelich.de/record/1027698/files/1-s2.0-S096980512200110X-main.pdf
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/1027698/files/1-s2.0-S096980512200110X-main.gif?subformat=icon
|x icon
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/1027698/files/1-s2.0-S096980512200110X-main.jpg?subformat=icon-1440
|x icon-1440
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/1027698/files/1-s2.0-S096980512200110X-main.jpg?subformat=icon-180
|x icon-180
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/1027698/files/1-s2.0-S096980512200110X-main.jpg?subformat=icon-640
|x icon-640
|y Restricted
909 C O |o oai:juser.fz-juelich.de:1027698
|p VDB
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 0
|6 P:(DE-Juel1)178654
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 1
|6 P:(DE-Juel1)185610
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 2
|6 P:(DE-Juel1)166419
913 1 _ |a DE-HGF
|b Key Technologies
|l Natural, Artificial and Cognitive Information Processing
|1 G:(DE-HGF)POF4-520
|0 G:(DE-HGF)POF4-525
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-500
|4 G:(DE-HGF)POF
|v Decoding Brain Organization and Dysfunction
|9 G:(DE-HGF)POF4-5253
|x 0
915 _ _ |a Nationallizenz
|0 StatID:(DE-HGF)0420
|2 StatID
|d 2023-08-22
|w ger
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b NUCL MED BIOL : 2022
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2023-08-22
915 _ _ |a No Peer Review
|0 StatID:(DE-HGF)0020
|2 StatID
|b ASC
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2023-08-22
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2023-08-22
915 _ _ |a IF < 5
|0 StatID:(DE-HGF)9900
|2 StatID
|d 2023-08-22
920 _ _ |l yes
920 1 _ |0 I:(DE-Juel1)INM-5-20090406
|k INM-5
|l Nuklearchemie
|x 0
980 _ _ |a conf
980 _ _ |a VDB
980 _ _ |a I:(DE-Juel1)INM-5-20090406
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21