动态PET揭示了分隔的大脑和肺组织,结核病药物的抗生素暴露
Xueyi Chen1,2,3, Bhavatharini Arun4, Oscar J Nino-Meza1,2,3
1Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
结核性脑膜炎的治疗方法使用新型成像显示了脑透的改善. 新的抗生素疗法在临床前模型中显示出有效性,优化了致命脑部感染的药物输送.
科学领域:
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
- 放射化学 放射化学是指辐射化学.
背景情况:
- 结核病 (TB) 是全球主要的死亡原因.
- 目前用于结核性脑膜炎的抗生素治疗方法没有优化进入大脑.
- 迫切需要有效治疗耐药结核病脑膜炎.
研究的目的:
- 通过使用动态PET,可视化18F-pretomanid在人类中的生物分布.
- 在临床前模型中确认优先分离抗生素到大脑或肺组织.
- 设计和评估针对结核病脑膜炎的优化,基于普雷托马尼德的治疗方案.
主要方法:
- 首次在人体上进行动态18F-前人胺PET成像,对8名受试者进行.
- 在感染的小鼠和子中使用抗生素放射类型的动态PET成像.
- 死后质谱和PET辅助的药物动力学建模.
- 在结核病脑膜炎的小鼠模型中对优化方案的评估.
主要成果:
- 在人类中,18F-前列曼尼德证明了优先分成大脑与肺组织.
- 在临床前模型中证实了优选的,针对抗生素的组织分区.
- PET建模预测了治疗性大脑暴露的人类剂量.
- 基于普雷托曼尼德的优化疗法在小鼠结核病脑膜炎模型中显示出优异的杀菌活性,而没有增加炎症或损伤.
- 大脑和肺组织中的不一致的抗生素活动与组织暴露相关.
结论:
- 动态PET成像为优化结核病脑膜炎治疗提供了对抗生素生物分布的见解.
- 优选的脑透是可以实现的,对于有效的结核病脑膜炎治疗至关重要.
- 这些发现支持开发针对脑膜炎和其他具有挑战性的感染的新型,隔间特定的抗生素策略.
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