Fluoroaniracetam: Initial Biodistribution and Characterization of a new Brain Imaging Agent

Objectives The racetam family of compounds have been used widely in the treatment of a central nervous system disorders ranging from alzheimer's to schizophrenia. The exact mechanism of action for these GABA derivative compounds is not well understood, however, they are known to bind to cholinergic receptors in the brain and may enable imaging of specific protein receptors and transporters. This work examines initial biodistribution and characteristics of a new fluorinated compound, N-[4-(2'-[¹⁸F]fluoroethyloxybenzoyl)]pyrrolidin-2-one (Fluoroaniracetam), for potential use in brain imaging applications.

Methods Fluoroaniracetam was developed and synthesized at the University of Tennessee and is currently under internal patent review. The compound was synthesized in three steps with a yield of nearly 35% and >97% radiochemical purity in our first runs. Healthy mice were dynamically imaged using microPET/CT. On the bed injection of 150 μCi was perfomed with data collection starting 10 seconds prior to injection. Listmode data were collected for 60 minutes and histogrammed into dynamic frames. Data were reconstructed using point spread function modeling with attenuation and scatter correction. Regions of interest were drawn in key organs, including the brain, liver, heart, and lungs. Time activity curves (TACs) were generated to assess biodistribution information.

Results TAC analysis indicates rapid biological clearance from all major organs with activity levels of < 3% in all major organs within 8 minutes. Peak activity in the brain of ~10 %ID/g was observed within 1.5 minutes of injection indicating a strong ability to cross the blood-brain barrier.

Conclusions Initial analyses show fast biological clearance of the compound. Peak brain values were found within 5 minutes with rapid entry into the brain. Further studies are needed to assess the complete biodistribution of this compound and to determine its possible use in brain imaging applications. This work indicates that fluoroaniracetam may be a possible candidate for PET brain imaging.

Research Support This work is funded by departmental funds of the Molecular Imaging and Translational Research Program of the University of Tennessee Graduate School of Medicine.