Universität zu Köln

Endepols, Heike, Zlatopolskiy, Boris D., Zischler, Johannes, Alavinejad, Nazanin, Apetz, Nadine ORCID: 0000-0003-3232-2517, Vus, Stefanie, Drzezga, Alexander and Neumaier, Bernd ORCID: 0000-0001-5425-3116 (2022). Imaging of cerebral tryptophan metabolism using 7-[F-18]FTrp-PET in a unilateral Parkinsonian rat model. Neuroimage, 247. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1095-9572

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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-[F-18]fluorotryptophan ([F-18]FTrp) to visualize all three pathways in a unilateral 6-OHDA rat model. [F-18]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-[F-18]FTrp-PET scans were conducted at different timepoints up to seven months after 6-OHDA injection. In addition, two 6-OHDA-injected rats were examined for neuroinflammation using [F-18]DAA1106-PET. 7-[F-18]FTrp-PET showed significantly increased tracer uptake at the 6-OHDA injection site which was negatively correlated to time after lesion placement. Accumulation of [F-18]DAA1106 at the injection site was increased as well, suggesting that 7-[F-18]FTrp uptake in this region may reflect kynurenine pathway activity associated with inflammation. Bilaterally in the dorsal hippocampus, 7-[F-18]FTrp uptake was significantly decreased and was inversely correlated to dopamine depletion severity, indicating that it reflects reduced serotonin synthesis. Finally, 7-[F-18]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-[F-18]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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Endepols, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Zlatopolskiy, Boris D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zischler, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Alavinejad, Nazanin UNSPECIFIED UNSPECIFIED UNSPECIFIED Apetz, Nadine UNSPECIFIED orcid.org/0000-0003-3232-2517 UNSPECIFIED Vus, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED orcid.org/0000-0001-5425-3116 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-588682
DOI:	10.1016/j.neuroimage.2021.118842
Journal or Publication Title:	Neuroimage
Volume:	247
Date:	2022
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1095-9572
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language KYNURENINE PATHWAY; MAMMALIAN BRAIN; PET-TRACERS; L-DOPA; SEROTONIN; DISEASE; MELATONIN; SYSTEM; LOCALIZATION; PROJECTIONS Multiple languages Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58868