PET/CT with [18F]ADAM using a biomarker for quantification of SERT change in the brain of PTSD rat model

Objectives Post-traumatic stress disorder (PTSD) is a psychiatric disorder which can occur after a traumatic event such as assault or disaster. It has been proven that serotonin transporter (SERT) is implicated in PTSD pathophysiology. However, there is little known the change of SERT on PTSD. In this study, we aimed to investigate the dynamitic change of SERT in the brain of PTSD rat with increasing severity of disease by using [18F]ADAM PET which reflects the SERT density.

Methods The PTSD rat model was built up based on Pavlovian fear conditioning. SD rats (N=6/group) were conditioned with 3, 6 and 10 tone-shock pairings at 1 min intervals, and the freezing behavior was measured the percentage of time spent in freezing during 1 min interval. The animals were preformed static PET imaging for 10 min after administration of [18F]ADAM (150 μCi, 100μl, i.v.) at 30 min. One day later, the animals were sacrificed, brains grounded for the measurement of AMPA receptor trafficking.

Results The freezing behavior increased during 3, 6 and 10 tone-shock presentation. The conditioned 6 or10 tone-shock pairings evoked much stronger freezing behavior compared with 3 tone-shock pairings groups (p < 0.01). Compared to sham rats, [18F]ADAM accumulations decreased in the amygdala and hippocampus in the PTSD rats with a fear intensity-dependent manner (Fig.1). The phosphorylation of GluR1 at Ser831 which were subunits of AMPA was dramatically increased in the hippocampus of fear conditioning group compared with control group.

Conclusions The results support that 4-[18F]-ADAM PET could be used to monitor the change of SERT associated with the status of phosphorylation of AMPA receptor in the brain in PTSD animal.

Research Support National Defense Medical Bureau