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@ARTICLE{Endepols:903942,
author = {Endepols, Heike and Zlatopolskiy, Boris and Zischler,
Johannes and Alavinejad, Nazanin and Apetz, Nadine and Vus,
Stefanie and Drzezga, Alexander and Neumaier, Bernd},
title = {{I}maging of cerebral tryptophan metabolism using
7-[18{F}]{FT}rp-{PET} in a unilateral {P}arkinsonian rat
model},
journal = {NeuroImage},
volume = {247},
issn = {1053-8119},
address = {Orlando, Fla.},
publisher = {Academic Press},
reportid = {FZJ-2021-05550},
pages = {118842 -},
year = {2022},
abstract = {Degradation products of the essential amino acid tryptophan
(Trp) are important signaling molecules in the mammalian
brain. Trp is metabolized either through the kynurenine
pathway or enters serotonin and melatonin syntheses. The aim
of the present work was to examine the potential of the
novel PET tracer 7-[18F]fluorotryptophan ([18F]FTrp) to
visualize all three pathways in a unilateral 6-OHDA rat
model. [18F]FDOPA-PET scans were performed in nine
6-OHDA-injected and six sham-operated rats to assess
unilateral dopamine depletion severity four weeks after
lesion placement. Afterwards, 7-[18F]FTrp-PET scans were
conducted at different timepoints up to seven months after
6-OHDA injection. In addition, three 6-OHDA-injected rats
and one healthy control were examined for neuroinflammation
using [18F]DAA1106-PET. 7-[18F]FTrp-PET showed significantly
increased tracer uptake at the 6-OHDA injection site which
was negatively correlated to time after lesion placement.
Accumulation of [18F]DAA1106 at the injection site was
increased as well, suggesting that 7-[18F]FTrp uptake in
this region may reflect kynurenine pathway activity
associated with inflammation. Bilaterally in the dorsal
hippocampus, 7-[18F]FTrp uptake was significantly decreased
and was inversely correlated to dopamine depletion severity,
indicating that it reflects reduced serotonin synthesis.
Finally, 7-[18F]FTrp uptake in the pineal gland was
significantly increased in relation with dopamine depletion
severity, providing evidence that melatonin synthesis is
increased in the 6-OHDA rat model. We conclude that
7-[18F]FTrp is able to detect alterations in both
serotonin/melatonin and kynurenine metabolic pathways, and
can be applied to visualize pathologic changes related to
neurodegenerative processes.},
cin = {INM-5 / INM-2},
ddc = {610},
cid = {I:(DE-Juel1)INM-5-20090406 / I:(DE-Juel1)INM-2-20090406},
pnm = {5253 - Neuroimaging (POF4-525)},
pid = {G:(DE-HGF)POF4-5253},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34942366},
UT = {WOS:000736962400011},
doi = {10.1016/j.neuroimage.2021.118842},
url = {https://juser.fz-juelich.de/record/903942},
}