Development of PET SERT agents in order to evaluate SERT availability in neuropsychiatric diseases may facilitate the use of PET as a predictive tool to select patients for SSRI treatment and monitor antidepressant therapy. A German Israeli Grant was obtained during 2005 for 3 years. (Joint German-Israeli Research Program, Development and clinical application of a PET-SERT ligand labeled with fluorine-18.)
Disturbances in serotonergic transmissions have been implicated in several neurological and psychiatric disorders. The serotonin transporter (SERT) has become the primary target of pharmacotherapy in neuropsychiatric diseases.
Selective serotonin reuptake inhibitors (SSRIs) bind with high selectivity and affinity to the SERT and increase synaptic serotonin levels.
However, the correlation between the degree of SERT occupancy in neuropsychiatric diseases and the clinical response to treatment by SERT blocking SSRIs need to be further investigated. To reliably quantify changes in SERT expression/function at the molecular level with positron emission tomography (PET), highly selective SERT radiotracers have to be developed. In order to test the final hypothesis that SERT availability is abnormal in patients with either obsessive compulsive disorder or depression, we have designed and developed novel labeled SERT radiotracers.
Their potential as PET brain imaging agents of regional SERT density will be evaluated by 1) in vitro measurements of SERT affinity and selectivity, 2) metabolic study in blood and brain (animal studies), 3) biodistribution measurement by ex vivo animal experiments 4) Micro-PET imaging of regional SERT distribution in the brain using animal models.
Up to now, no optimal methods including PET can determine accurately to what extent the serotonergic system is affected in neuropsychiatric disorders. We are currently developing novel PET radiotracers that could be used to measure SERT availability and its occupancy by SSRIs in vivo.
Correlation between SERT regional levels measured by PET using our radiotracer and SSRI treatment efficiency may facilitate the use of PET as a predictive tool to select patients for SSRI treatment and monitor antidepressant therapy.