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Development and Evaluation of Two Potential 5-HT7 Receptor PET Tracers: [18F]ENL09 and [18F]ENL10

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  1. Classics in Neuroimaging: The Serotonergic 2A Receptor System-from Discovery to Modern Molecular Imaging

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  2. Synthesis and in vitro evaluation of oxindole derivatives as potential radioligands for 5-HT(7) receptor imaging with PET

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  1. Optimization of preprocessing strategies in Positron Emission Tomography (PET) neuroimaging: A [11C]DASB PET study

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  2. Microdosing psychedelics: More questions than answers? An overview and suggestions for future research

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  3. Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions

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  4. Association Between Sumatriptan Treatment During a Migraine Attack and Central 5-HT1B Receptor Binding

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The latest addition to the serotonin (5-HT) receptor family is the 5-HT7 receptor (5-HT7R). This receptor has gained interest as a drug target due to its involvement in various disorders such as depression or schizophrenia. There is currently no clinically validated positron emission tomography (PET) tracer for the 5-HT7R available. But, the (arylpiperazinyl-butyl)oxindole scaffold provides a promising lead structure for this purpose. Here, we synthesized 12 (arylpiperazinyl-butyl)oxindole derivatives and in vitro affinity screening identified two structures with suitable affinity and selectivity to be radiolabeled and tested as 5-HT7R selective PET tracers. Next, the radiolabeled products [18F]ENL09 and [18F]ENL10 were evaluated as PET tracers in rats. Both tracers were found to be P-gp substrates, but after P-gp inhibition the brain uptake showed a regional distribution in line with the known 5-HT7R distribution. The [18F]ENL10 brain binding was displaceable with a 5-HT7R selective ligand, whereas [18F]ENL09 was not. We find that [18F]ENL10 is a promising 5-HT7R selective PET tracer candidate that should be investigated in higher species.

Original languageEnglish
JournalACS Chemical Neuroscience
Volume10
Issue number9
Pages (from-to)3961-3968
Number of pages8
ISSN1948-7193
DOIs
Publication statusPublished - 18 Sep 2019

ID: 58486546