Purpose: Olanzapine (OLZ) is an atypical antipsychotic agent that is characterized by low brain porousness. The present work aimed to develop radiolabeled olanzapine (OLZ) without colloidal impurities and evaluate its biodistribution following intravenous (I.V.) and intranasal (I.N.) administration as a potential agent for brain diagnosis.

Materials and methods: OLZ was radiolabeled with technetium-99m by using sodium dithionite as the reducing agent. Biodistribution of ^99mTc-OLZ complex in mice following I.V. and I.N. administrations was examined. Furthermore, a molecular docking study was performed.

Results: Sodium dithionite labeling procedure resulted in highest radiochemical yield (96.30 ± 0.09%) and in vitro stability in serum up to 8 h. Biodistribution study of ^99mTc-OLZ complex showed high brain uptake following I.N. (6.2 ± 0.12% ID/g) and I.V. (5.5 ± 0.09% ID/g) at 0.5 and 1 h post administration (P.I.), respectively. Docking into two brain targets predicts higher affinity of ^99mTc-OLZ than free OLZ. Additionally, docking to P-glycoproteins shows less affinity for the radiolabelled OLZ and hence it is expected to be associated with better brain exposure than free OLZ.

Conclusion: These chemical and preliminary biological merits strongly suggest that the ^99mTc-OLZ complex with new reducing agent could be used as a potential diagnostic agent for brain.

目的：奥氮平（OLZ）是一种非典型的抗精神病药，其特征是脑部疏松程度低。本工作旨在开发不含胶体杂质的放射性标记的奥氮平（OLZ），并评估静脉（IV）和鼻内（IN）给药后其生物分布，将其作为脑诊断的潜在药物。

材料与方法：以连二亚硫酸钠为还原剂，用tech 99m放射性标记OLZ。在静脉和静脉内给药后，检查了^99m Tc-OLZ复合物在小鼠中的生物分布。此外，进行了分子对接研究。

结果：连二亚硫酸钠标记程序可产生最高的放射化学产率（96.30±0.09％），并在长达8 h的血清中具有体外稳定性。对^99m Tc-OLZ复合物的生物分布研究表明，分别在给药后（PI）0.5和1 h，IN（6.2±0.12％ID / g）和IV（5.5±0.09％ID / g）后高脑摄取。对接到两个大脑靶标中，预测^99m Tc-OLZ的亲和力要高于游离OLZ。另外，与P-糖蛋白的对接显示出对放射性标记的OLZ的亲和力较小，因此，与游离OLZ相比，其与更好的脑暴露相关。

结论：这些化学和初步生物学优点强烈表明，带有新型还原剂的^99m Tc-OLZ复合物可以用作脑的潜在诊断剂。