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 ([I]BO-1, [I]BO-2, and [I]BT-2) displayed moderate brain uptake (2.7, 2.9, and 2.8% ID/g, respectively) at 2 min postinjection. On autoradiography using normal mice, [I]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 [I]BO-2 was reduced in the lysophosphatidylcholine-induced demyelination region. In conclusion, [I]BO-2 demonstrated the fundamental characteristics of a myelin imaging probe for SPECT.

中文翻译：

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用于多发性硬化症髓磷脂成像的放射性碘化苯并恶唑和苯并噻唑衍生物的合成和生物学评价

多发性硬化症 (MS) 是一种中枢神经系统慢性炎症性疾病，由髓鞘破坏引起。由于多发性硬化症的症状和病程具有异质性，定期监测疾病活动对于诊断和治疗非常重要。在本研究中，我们合成了四种放射性碘化苯并恶唑（BO）和苯并噻唑（BT）衍生物，并评估了它们作为单光子发射计算机断层扫描（SPECT）的新型髓磷脂成像探针的实用性。在使用正常小鼠的生物分布研究中，三种化合物（[I]BO-1、[I]BO-2 和 [I]BT-2）显示出中等的脑摄取量（分别为 2.7%、2.9% 和 2.8% ID/g） ）在注射后 2 分钟。在使用正常小鼠的放射自显影中，[I]BO-2 显示白质（髓磷脂丰富区域）与灰质（髓磷脂缺乏区域）中放射性积累的最佳比率。此外，[I]BO-2的放射性在溶血磷脂酰胆碱诱导的脱髓鞘区域中降低。总之，[I]BO-2 展示了 SPECT 髓磷脂成像探针的基本特征。