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@INPROCEEDINGS{Kolks:865320,
author = {Kolks, N. and Zlatopolskiy, BD and Urusova, EA and
Neumaier, B.},
title = {{S}ynthesis of {N}-methyl- and
5-{HO}-[18{F}]fluorotryptophans},
reportid = {FZJ-2019-04822},
year = {2019},
abstract = {Ziel/Aim:Tryptophan (Trp) metabolism is altered in numerous
pathological processes. 7-[F-18]FTrp developed in our group
is a promising PET-tracer for imaging of Trp metabolism but
is unable to distinguish between the two pathways of Trp
metabolization. The aim of this project was the development
of procedures for the preparation of NinMe-6- and
5-HO-7-[F-18]FTrp as PET-probes suitable for selective
visualization of the kynurenine or serotonin
pathway.Methodik/Methods:Precursor for the radiosynthesis of
NinMe-6-[F-18]FTrp, (S,S)-BPB-Ni-NinMe-6-Bpin-Trp, was
synthesized starting from 6-bromoindole. Miyaura borylation,
followed by a Mannich reaction and quaternization with MeI
furnished
N,N,N-(6-Bpin-NinMe-indolyl)methyltrimethylammonium iodide.
Alkylation of (S)-BPB-Ni-Gly with the latter and
Nin-methylation afforded the desired precursor.
Boc-7-Bpin-5-AcO-Trp-OtBu was prepared via Ir-catalyzed
2,7-diborylation of Boc-5-AcO-Trp-OtBu, accessible from
5-OH-Trp in three reaction steps, followed by selective
2-deborylation using Bi(OAc)3. Both precursors were
radiolabeled according to the protocol of alcohol-enhanced
Cu-mediated F-18-fluorination. The decomposition of the
labeled precursors under acidic conditions afforded the
F-18-labeled amino acids NinMe-6- and
5-HO-7-[F-18]FTrp.Ergebnisse/Results:(S,S)-BPB-Ni-NinMe-6-Bpin-Trp
was obtained in a total yield of $13\%$ after 5 steps and
Boc-7-BPin-5-AcO-Trp-OtBu in a $12\%$ yield after 5 steps.
(S,S)-BPB-Ni-NinMe-6-[F-18]FTrp was produced in RCCs of up
to $90\%,$ decomposed to Nin-Me-6-[F-18]FTrp and isolated by
HPLC in RCY of 10 – $15\%.$ Boc-5-OAc-7-Bpin-Trp-OtBu was
labeled with an RCC of $25\%$ and after deprotection
5-HO-7-[F-18]FTrp was obtained similarly to
NinMe-6-[F-18]FTrp but in lower
RCY.Schlussfolgerungen/Conclusions:Nin-Me-6- and
5-HO-7-[F-18]FTrp represent promising PET-probes for the
delineation of kynurenine and serotonin pathways of Trp
metabolism. Both probes were successfully prepared using
alcohol-enhanced Cu-mediated radiofluorination.},
month = {Apr},
date = {2019-04-03},
organization = {57. Jahrestagung der Deutschen
Gesellschaft für Nuklearmedizin,
Bremen (Germany), 3 Apr 2019 - 6 Apr
2019},
subtyp = {After Call},
cin = {INM-5},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {573 - Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)6},
doi = {10.1055/s-0039-1683491},
url = {https://juser.fz-juelich.de/record/865320},
}