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Author Notes:

To whom correspondence should be addressed. Department of Radiology, Emory University, 1364 Clifton Road NE, Atlanta, GA 30322 Phone: (404) 727-9366. Fax: (404) 727-3488. E-mail: mgoodma@emory.edu.

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Research Funding:

National Institute of Mental Health : NIMH

This research was sponsored by the NIMH (1-R21-MH-66622-01).

We acknowledge the use of shared instrumentation provided by grants from the NIH and the NSF.

Synthesis, Radiosynthesis, and Biological Evaluation of Fluorine-18 Labeled 2?-Carbo(fluoroalkoxy)-3?-(3?-((Z)-2-haloethenyl)phenyl)nortropanes: Candidate Radioligands for In Vivo Imaging of the Serotonin Transporter with Positron Emission Tomography

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Journal Title:

Journal of Medicinal Chemistry

Volume:

Volume 51, Number 24

Publisher:

, Pages 7788-7799

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The meta-vinylhalide fluoroalkyl ester nortropanes 1-4 were synthesized as ligands of the serotonin transporter (SERT) for use as positron emission tomography (PET) imaging agents. In vitro competition binding assays demonstrated that 1-4 have a high affinity for the SERT (Ki's = 0.3 - 0.4 nM) and are selective for the SERT over the dopamine and norepinephrine transporters (DAT and NET). MicroPET imaging in anesthetized cynomolgus monkeys with [18F]1-[18F]4 demonstrated that all four tracers behave similarly with peak uptake in the SERT-rich brain regions achieved after 45-55 min followed by a steady washout. An awake monkey study was performed with [18F]1 which demonstrated that the uptake of [18F]1 was not influenced by anesthesia. Chase studies with the SERT ligand 15 displaced [18F]1-[18F]4 but chase studies with the DAT ligand 16 did not displace [18F]1-[18F]4 thus indicating that the tracers were binding specifically to the SERT.

Copyright information:

© 2008 American Chemical Society

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