TY  - JOUR
AU  - Endepols, Heike
AU  - Zlatopolskiy, Boris
AU  - Zischler, Johannes
AU  - Alavinejad, Nazanin
AU  - Apetz, Nadine
AU  - Vus, Stefanie
AU  - Drzezga, Alexander
AU  - Neumaier, Bernd
TI  - Imaging of cerebral tryptophan metabolism using 7-[18F]FTrp-PET in a unilateral Parkinsonian rat model
JO  - NeuroImage
VL  - 247
SN  - 1053-8119
CY  - Orlando, Fla.
PB  - Academic Press
M1  - FZJ-2021-05550
SP  - 118842 -
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34942366
UR  - <Go to ISI:>//WOS:000736962400011
DO  - DOI:10.1016/j.neuroimage.2021.118842
UR  - https://juser.fz-juelich.de/record/903942
ER  -