Radio-Halogenated Flurobutenyl Tropanes for Imaging Dopamine Transporters

Emory University
posted on 07/07/2009

Applications

Imaging of dopamine transporters for drug development, research, diagnosis and treatment of CNS diseases and disorders such as Parkinson's disease and controlled substance addiction.

Highlights

Diagnostic imaging agents bind with high affinity to the dopamine transporter (DAT).
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

Dopamine transporters are proteins that reside on the membrane of the nerve terminals of the presynaptic mesolimbic dopaminergic neurons. The DAT serves to remove dopamine from the synapse, a process which helps regulate CNS dopamine neurotransmission. DAT density level has been associated with Parkinson's disease. A radio-labeled analog that binds the dopamine transporter is an excellent candidate diagnostic radiopharmaceutical for diagnosis and treatment management of Parkinson's disease. It can also be used for treatment management of cocaine addiction.

The invention relates to a new series of brain imaging agents, N-(E)-4'-fluorobut-2-en-1-yl-2b-carbomethoxy -3b-(4-substituted-pheny) nortropane (FBNT). FBNT, when labeled with a positron emitting radioisotope such as 18F, can be used as a diagnostic imaging agent to measure central nervous system (CNS) neuronal function in the brain of patients suffering from Parkinson's disease and cocaine addiction. This tropane was designed to bind with high affinity to the dopamine transporter (DAT). FBCINT exhibits higher specific binding (i.e., greater than 12:1) striatal to cerebellum and striatal to cortex ratio in non-human primates) compared to any other reported PET DAT imagine agent. In addition, FBCINT reaches a transient equilibrium with DAT sites in the stratum which allows for quantitative determination of the number of DAT sites within a normal imaging session of 2 hours.