Imaging of changes in norepinephrine transporter in depression model rats with a radiobrominated (2S,αS)-2-(α-(2-bromophenoxy)benzyl)morpholine

Objectives Changes in norepinephrine transporter (NET) in the brain have been suggested to be a causative factor of major depression. Accordingly, imaging of NET expression in the brain should help clarifying the etiology of depression and monitoring therapeutic efficacy. Recently, we synthesized a tracer, radiobrominated (2S,αS)-2-(α-(2-bromophenoxy)benzyl)morpholine ((SS)-BPBM) for imaging NET functions. Therefore, we evaluated the possibility of the tracer to image the changes in NET functions in depression model rats.

Methods Nno-carrier-added (SS)-[⁷⁷Br]BPBM was synthesized by a iodine-radiobromine exchange reaction. As depression model rats, zinc deficient rats were used. For assessing regional changes in accumulation of (SS)-[⁷⁷Br]BPBM, ex vivo autoradiography were preformed. The regional accumulation was expressed as distribution absorption ratio (DAR), an index of radiotracer accumulation corrected by body weight.

Results The radiochemical yield of (SS)-[⁷⁷Br]BPBM was about 45% and the radiochemical purity was greater than 99%. In the locus coeruleus (LC), which is the richest region of NET expression, the accumulation of (SS)-[⁷⁷Br]BPBM significantly decreased in depression model rats compared with control rats (control: 2.48 ± 0.44, depression model: 1.78 ± 0.78, P<0.05). On the other hand, the accumulation in the cortex was significantly increased in the depression model compared with control group (control: 0.20 ± 0.04, depression model: 0.33 ± 0.03, P<0.001). In other brain regions there were no significant differences between two groups.

Conclusions Changed NET expression in the LC and cortex regions was detected with a radiobrominated (SS)-BPBM in depression model rats. Radiobrominated (SS)-BPBM provides a potential means for investigating depression.