无螯合剂超小碘化[64Cu]Cu纳米团簇用于肺癌精准PET/CT成像及放射治疗

PET/CT是肺癌早期诊断和分期的重要手段。然而临床常规使用的18F-FDG在诊断灵敏度和特异性方面存在一定局限性。目前新分子探针的研究多采用纳米粒的表面修饰上放射性金属螯合物，但纳米粒的物理化学特性可能因此受到影响，导致所检测的放射性不能真正反映纳米粒的体内过程；另有研究采用的是 64Cu与大环螯合剂形成稳定复合物，标记于各种纳米粒、肽或者抗体，但缺点是体内稳定性差。针对上述方法存在的问题，本课题以牛血清白蛋白(BSA)为模板，通过一锅化学还原法合成放射性[64Cu]Cu纳米团簇，同时在该纳米团簇的外壳BSA蛋白上络合能够增强CT成像的碘，BSA壳层又偶联了肺癌靶向核酸适配体GLT21.T，生成无螯合剂超小碘化[64Cu]Cu纳米团簇。无螯合剂超小碘化[64Cu]Cu纳米团簇PET/CT成像有望提高肺癌的诊断效能。64Cu产生的β-粒子还可能实现PET/CT成像引导下的肿瘤内放射治疗。

PET/CT is an important method of early diagnosis and staging of lung cancer. However, the conventional use of 18F-FDG have some limitations of diagnostic sensitivity and specificity. At present, the surface of nanoparticles is modified by radioactive metal chelates, but the physical chemistry properties of nanoparticles may be affected, as a result, the detected radioactivity does not really reflect the in Vivo process of the nanoparticles. Another study used 64Cu to form a stable complex about macrocyclic chelators, labeled with various nanoparticles, peptides or antibodies, but the disadvantage is poor in Vivo stability. In order to solve the problems of the above methods , the 64Cu nanoclusters were synthesized by one pot chemical reduction method using bovine serum albumin as template , at the same time , the binding of iodine with BSA can enhance CT imaging , and the BSA Shell is coupled with the lung cancer targeting Aptamer GLT21.T, the formation of 64Cu nanoclusters without chelating agent was studied . Non-chelating agent-free ultra-small iodide 64Cu nanocluster PET/CT imaging is expected to improve the diagnostic efficiency of lung cancer. The Beta-particle produced by 64Cu may also be used in PET/CT guided radiotherapy.