案例信息

标题：放射卫生防护的教学思考

【专业学位类别】公共卫生

【专业领域/方向】转化医学

【作者】郭志德

【单位】厦门大学公共卫生学院

【关键词】辐射；放射性药物；放射生物学效应；放射防护

【适用课程】转化医学选论

【案例摘要】

基于免疫抗体载体的放射性药物在肿瘤等重大疾病诊疗中的价值日益突出，潜力巨大。然而，核素的多器官分布及体内长时间残留等弊端一直未能有效解决，伴随的组织辐照伤害也需审慎考虑。基于此，本项目提出了基于生物正交剪切及肾脏酶切双调控机制的放射性药物设计策略，为提升探针功能及核素体内促排提供了独特的解决方案。具体来说，通过可用于核素标记的多功能连接子修饰抗体分子。多功能连接子可实现双源分步的核素清除策略，其具有能被肾脏中性内肽酶识别的特定多肽序列以及可发生剪切反应的四嗪基团。在定点清除肾脏滞留核素的同时，可通过引入外源环辛烯配套药盒调控探针药代动力学行为。这种新型、智能的探针结构，以及内外双源调控剪切的核素清除策略，有望解决当前众多核药物的共同不足，引领更为安全、绿色、高效的核药诊疗平台建设，具有重要的理论和实践意义。

Title: Throughts on Radiological Protection

Professional Degree Category: Master of Public Health

Specialized fields: Translational Medicine

Authors: Zhide Guo

Affiliation: School of Public Health, Xiamen University

Key words: Radiation; Radiopharmaceuticals; Radiobiological effect; Radiation protection

Abstract

The great success of radiopharmaceuticals based on immune antibody has initiated a new phase in the theranostics of major diseases. However, the high and persistent entrails accumulation of radioactivity remains a challenge for clinical practice and safe. This highlights a need for probe promotion and novel decorporation. In this study, radiotheranostics are designed by integrating the strategy of bioorthogonal cleavage reaction and enzyme-mediated degradation for the theranostic application. We aim to develop a multifunctional chelator (MFC) to label antibodies with radionuclide. The MFK sequence in MFC can be recognized by brush border membrane vesicles (BBMVs) and cleaved at the amide bond between Met and Val, thus releasing the small fragment containing radionuclide. As a result, more favorable tumor-to-non-target ratios can be achieved. At the same time, triggered radionuclide release from the parent substance can be accomplished by the biorthogonal “click-to-release” chemistry employing MFC-conjugated tetrazine (Tz) and exogenous trans-cyclooctenes (TCO). This new intellectual design stratagem is expected to overcome the most of shortages of current radiopharmaceuticals, and fulfilling its value as a platform for high-quality probes developing in the future.

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