Synthesis and biological evaluation of radioiodinated benzoxazole and benzothiazole derivatives for imaging myelin in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that results from destruction of the myelin sheath. Due to heterogeneity of the symptoms and course of MS, periodic monitoring of disease activity is important for diagnosis and treatment. In the present study, we synthesized four radioiodinated benzoxazole (BO) and benzothiazole (BT) derivatives, and evaluated their utility as novel myelin imaging probes for single photon emission computed tomography (SPECT). In a biodistribution study using normal mice, three compounds ([125I]BO-1, [125I]BT-2, and [125I]BO-2) displayed moderate brain uptake (2.7, 2.9, and 2.8 % ID/g, respectively) at 2 min postinjection. On ex vivo autoradiography using normal mice, [125I]BO-2 showed the most preferable ratio of radioactivity accumulation in white matter (myelin-rich region) versus gray matter (myelin-deficient region). In addition, the radioactivity of [125I]BO-2 was reduced in the LPC-induced demyelination region. In conclusion, [123I]BO-2 demonstrated the fundamental characteristics of a myelin imaging probe for SPECT.