Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Development and Evaluation of Two Potential 5-HT7Receptor PET Tracers: [18F]ENL09 and [18F]ENL10

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Glucagon-like peptide-1 receptor regulation of basal dopamine transporter activity is species-dependent

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Imaging HDACs In Vivo: Cross-Validation of the [11C]Martinostat Radioligand in the Pig Brain

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Dynamic coupling of whole-brain neuronal and neurotransmitter systems

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Serotonin release measured in the human brain: a PET study with [11C]CIMBI-36 and d-amphetamine challenge

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftACS Chemical Neuroscience
Vol/bind10
Udgave nummer9
Sider (fra-til)3961-3968
Antal sider8
ISSN1948-7193
DOI
StatusUdgivet - 18 sep. 2019

ID: 58486546