Development and Evaluation of Two Potential 5-HT7 Receptor PET Tracers: 18FENL09 and 18FENL10.

08:00 EDT 11th April 2019 | BioPortfolio

Summary of "Development and Evaluation of Two Potential 5-HT7 Receptor PET Tracers: 18FENL09 and 18FENL10."

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 radiolabelled and tested as 5-HT7R selective PET tracers. Next, the radiolabelled 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 and [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.


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This article was published in the following journal.

Name: ACS chemical neuroscience
ISSN: 1948-7193


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