Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215000, China.
ACS Appl Mater Interfaces. 2022 Feb 23;14(7):8838-8846. doi: 10.1021/acsami.1c23907. Epub 2022 Feb 8.
Nuclear medicine imaging has aroused great interest in the design and synthesis of versatile radioactive nanoprobes, while most of the methods developed for radiolabeling nanoprobes are difficult to satisfy the criteria of clinical translation, including easy operation, mild labeling conditions, high efficiency, and high radiolabeling stability. Herein, we demonstrated the universality of a simple but efficient radiolabeling method recently developed for constructing nuclear imaging nanoprobes, that is, ligand anchoring group-mediated radiolabeling (LAGMERAL). In this method, a diphosphonate-polyethylene glycol (DP-PEG) decorating on the surface of inorganic nanoparticles plays an essential role. In principle, owing to the strong binding affinity to a great variety of metal ions, it can not only endow the underlying nanoparticles containing metal ions including some main group metal ions, transition metal ions, and lanthanide metal ions with excellent colloidal stability and biocompatibility but also enable efficient radiolabeling through the diphosphonate group. Based on this assumption, inorganic nanoparticles such as FeO nanoparticles, NaGdF:Yb,Tm nanoparticles, and CuS nanoparticles, as representatives of functional inorganic nanoparticles suitable for different imaging modalities including magnetic resonance imaging (MRI), upconversion luminescence imaging (UCL), and photoacoustic imaging (PAI), respectively, were chosen to be radiolabeled with different kinds of radionuclides such as SPECT nuclides (e.g., Tc), PET nuclides (e.g., Ga), and therapeutic SPECT nuclides (e.g., Lu) to demonstrate the reliability of the LAGMERAL approach. The experimental results showed that the obtained nanoprobes exhibited high radiolabeling stability, and the whole radiolabeling process had negligible impacts on the physical and chemical properties of the initial nanoparticles. Through passive targeting SPECT/MRI of glioma tumor, active targeting SPECT/UCL of colorectal cancer, and SPECT/PAI of lymphatic metastasis, the outstanding potentials of the resulting radioactive nanoprobes for sensitive tumor diagnosis were demonstrated, manifesting the feasibility and efficiency of LAGMERAL.
核医学成像激发了人们对多功能放射性纳米探针设计和合成的极大兴趣，而大多数为放射性标记纳米探针开发的方法都难以满足临床转化的标准，包括操作简单、标记条件温和、效率高和放射性标记稳定性高。在此，我们展示了一种最近开发的用于构建核医学成像纳米探针的简单但高效的放射性标记方法——配体锚定基团介导的放射性标记（LAGMERAL）的通用性。在该方法中，表面修饰的二膦酸-聚乙二醇（DP-PEG）发挥了重要作用。原则上，由于其与各种金属离子具有很强的结合亲和力，不仅可以赋予包含金属离子的基础纳米粒子以优异的胶体稳定性和生物相容性，这些金属离子包括一些主族金属离子、过渡金属离子和镧系金属离子，还可以通过二膦酸基团实现高效放射性标记。基于这一假设，分别选择了 FeO 纳米粒子、NaGdF:Yb,Tm 纳米粒子和 CuS 纳米粒子等功能无机纳米粒子作为代表，它们适用于不同的成像模式，包括磁共振成像（MRI）、上转换发光成像（UCL）和光声成像（PAI），并用不同的放射性核素如 SPECT 核素（如 Tc）、PET 核素（如 Ga）和治疗性 SPECT 核素（如 Lu）对其进行放射性标记，以证明 LAGMERAL 方法的可靠性。实验结果表明，所得到的纳米探针具有高放射性标记稳定性，整个放射性标记过程对初始纳米粒子的物理化学性质几乎没有影响。通过脑胶质瘤肿瘤的被动靶向 SPECT/MRI、结直肠癌的主动靶向 SPECT/UCL 和淋巴转移的 SPECT/PAI，证明了所得放射性纳米探针在灵敏肿瘤诊断方面的优异潜力，表明了 LAGMERAL 的可行性和效率。
