新型氟-18标记心脏神经显像药物的研制及PET显像研究

The dysfunction of autonomic nervous system (ANS) is closely related to the pathogenesis and prognosis of acute and chronic myocardial ischemia, heart failure and other common diseases. It is difficult to directly test the changes of the ANS with imaging technology, such as CT and MRI. Although the radionuclide imaging technology can carry on effective detection to the ANS changes, it is difficult to carry out in the country due to lack of an ideal imaging radiopharmaceuticals or restricted supply of radionuclide. The project will design a series of novel 18F labeled cardiac neuronal imaging agent，the characteristic of the structure is leading-in PEGs or nitrogen phospholipids and sulfonyl on the basis of norepinephrine analogue 's functional groups. We will screened out a cardiac neuronal imaging agent whose characteristic is simple to preparing and optimal in terms of biological properties, its validity and practicability can be demonstrated by PET imaging in animal models with myocardial ischemia or heart failure. The project developed a cardiac neuronal imaging agent with independent intellectual property rights which promise to provide a new and effective technique for early diagnosis and prognosis of ANS-related heart disease and preliminary lay the clinical foundation for achieving the goal of transforming in the future.

心脏自主神经系统（autonomic nervous system, ANS）功能完整性的损伤与急慢性心肌缺血、心力衰竭等常见心脏疾病的早期发病机制及预后密切相关。CT、MRI等影像学技术难以直接观察到ANS的变化。核素显像技术虽然能够对ANS变化进行有效监测，但由于缺乏理想的显像药物或是受到标记核素供应的限制，目前在国内难以开展。本项目在于构建一系列新型的心脏神经显像药物，其结构特征是在去甲肾上腺素类似物胍乙啶功能基团的基础上，引入聚乙二醇链或氮磷脂及氮磺酰基，并进行18F标记。通过放射化学性质测定及动物实验研究从中筛选出一种制备简便、生物学性能最佳的心脏神经显像药物，并以心肌缺血及心衰动物模型的PET显像证实其有效性和实用性。本项目研制的显像药物具有自主知识产权，有希望为ANS相关心脏疾病的早期诊断和预后评估提供新的有效的技术手段，并为未来实现临床转化的目标初步奠定基础。

心脏自主神经系统（autonomic nervous system, ANS）功能完整性的损伤与急慢性心肌缺血、心力衰竭等常见心脏疾病的早期发病机制及预后密切相关。CT、MRI等影像学技术难以直接观察到ANS的变化。核素显像技术虽然能够对ANS变化进行有效监测，但由于缺乏理想的显像药物或是受到标记核素供应的限制，目前在国内难以开展。本项目在于构建一系列新型的心脏神经显像药物，其结构特征是在去甲肾上腺素类似物胍乙啶功能基团的基础上，引入聚乙二醇链或氮磷脂及氮磺酰基，并进行18F标记。通过放射化学性质测定及动物实验研究从中筛选出一种制备简便、生物学性能最佳的心脏神经显像药物，并以心肌缺血及心衰动物模型的PET显像证实其有效性和实用性。其中，化合物18F-FP2BG在大鼠及中华小型猪中心肌摄很高，肝肺本底较低，性能优良。本项目研制的显像药物具有自主知识产权，有希望为ANS相关心脏疾病的早期诊断和预后评估提供新的有效的技术手段，并为未来实现临床转化的目标初步奠定基础。