Radio-Halogenated Nortropanes for Imaging Serotonin Transporters

Emory University
posted on 07/07/2009

Applications

Imaging of serotonin transporters for drug development and research pertaining to central nervous system (CNS) diseases and disorders.

Highlights

Diagnostic imaging agents bind with high affinity to the serotonin transporter (SERT).
Useful for measuring neuronal function in the brain of patients suffering from various diseases and disorders of the CNS including major depression, obsessive compulsive disorder and drug addiction.

Technical Summary

The serotonin and norepinephrine transporters are proteins that reside on the membrane of the nerve terminals of the serotoninergic neurons. The SERT removes serotonin from the synapse, a process which helps regulate CNS neurotransmission. This transporter has been convincingly implicated in the pathophysiology of major depression and represents the putative site of action for the majority of antidepressant medications. In addition, abnormalities in SERT density in the midbrain and frontal cortex have also been associated with obsessive compulsive disorder. Supporting evidence or the role of SERT in these diseases, however, has been predominantly collected in heterogeneous cell models of transporter function and from post-mortem human tissue.

The present invention describes halogen-labeled compounds in the 4-fluoroalkyl-3-halophenyl nortropane family that can be used to image serotonin receptor function in vivo.These compounds use a fluoride isotope that gives the labeled compounds a more useful half-life and higher resolution than previous studies performed with carbon isotopes. The nortropanes demonstrate pronounced brain uptake, low non-specific binding and high SERT selectivity and affinity. The compounds can be used to diagnose major affective disorders and may be used to differentiate for example, depression from other psychiatric disorders.