Imaging of cerebral tryptophan metabolism using 7-[18F]FTrp-PET in a unilateral Parkinsonian rat model

Heike Endepols; Boris D. Zlatopolskiy; Johannes Zischler; Nazanin Alavinejad; Nadine Apetz; Stefanie Vus; Alexander Drzezga; Bernd Neumaier

NeuroImage (Feb 2022)

Imaging of cerebral tryptophan metabolism using 7-[18F]FTrp-PET in a unilateral Parkinsonian rat model

Heike Endepols,
Boris D. Zlatopolskiy,
Johannes Zischler,
Nazanin Alavinejad,
Nadine Apetz,
Stefanie Vus,
Alexander Drzezga,
Bernd Neumaier

Affiliations

Heike Endepols: University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Str. 62, 50937 Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine, Kerpener Str. 62, 50937 Cologne, Germany; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52425 Jülich, Germany
Boris D. Zlatopolskiy: University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Str. 62, 50937 Cologne, Germany; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52425 Jülich, Germany
Johannes Zischler: University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Str. 62, 50937 Cologne, Germany; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52425 Jülich, Germany
Nazanin Alavinejad: University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Str. 62, 50937 Cologne, Germany
Nadine Apetz: University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Str. 62, 50937 Cologne, Germany
Stefanie Vus: University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Str. 62, 50937 Cologne, Germany; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52425 Jülich, Germany
Alexander Drzezga: University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine, Kerpener Str. 62, 50937 Cologne, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germany; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Molecular Organization of the Brain (INM-2), Wilhelm-Johnen-Straße, 52425 Jülich, Germany
Bernd Neumaier: University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Str. 62, 50937 Cologne, Germany; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52425 Jülich, Germany; Max Planck Institute for Metabolism Research, Cologne 50931, Germany; Corresponding author at: Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52425 Jülich, Germany.

Journal volume & issue: Vol. 247
p. 118842

Abstract

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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, two 6-OHDA-injected rats 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.

Published in NeuroImage

ISSN: 1053-8119 (Print); 1095-9572 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neuroimage

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