Inherently PET/CT Dual Modality Imaging Lipid Nanocapsules for Early Detection of Orthotopic Lung Tumors
Inherently PET/CT Dual Modality Imaging Lipid Nanocapsules for Early Detection of Orthotopic Lung Tumors
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DOI：
10.1021/acsabm.9b00993
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发表时间：
2020-01-21
影响因子：
4.7
通讯作者：
Gao, Xueyun
中科院分区：
文献类型：
--
作者：
Cai, Pengju;Su, Dongdong;Gao, Xueyun
早期癌症的准确诊断是降低癌症死亡率和提高生存率的关键。PET成像灵敏度高，但空间分辨率低，而CT成像具有良好的空间位置信息。因此，PET和CT成像的结合可以提供互补的优势，以实现肿瘤的准确早期诊断。然而，目前开发的PET或CT成像剂仅具有单一功能。在这里，我们设计并构建了一种自组装的脂质纳米胶囊与碘克沙醇封装和标记的自螯合Cu-64的微小肺肿瘤的精确PET/CT成像。脂质纳米胶囊使用LPPC-Ce 6（二氢卟酚e6（Ce 6）和溶血磷脂酰胆碱（LPPC）的缀合物）在水中自组装以形成双层囊泡结构。Cu-64通过对Cu ~（2+）的天然捕获能力嵌入Ce_6的四吡咯环中心。将靶向肺癌的适体GLT 21.T缀合至脂质纳米胶囊的表面。将碘克沙醇装载到脂质纳米胶囊（Cu-64@LCI-apt）的空腔中。在纳米结构中，碘克沙醇的负载量足够高，并且可以根据成像要求灵活地调节比活性。制备的Cu-64@LC1-apt具有良好的放射性标记效率、稳定性和对肺肿瘤的有效靶向性。在早期原位肺癌模型中，Cu-64@LCI-apt证明了灵敏的PET成像和增强对比CT成像的能力，从而能够对直径为500 μ m的微小原位肺肿瘤进行有效的高质量PTE/CT成像。Cu-64@LCI-apt具有通过双模式PET/CT成像对肿瘤进行早期、灵敏和准确诊断的巨大潜力。
Accurate diagnosis of cancer at an early stage is the key to reduce cancer mortality and improve survival. PET imaging has high sensitivity but low spatial resolution, while CT imaging has good spatial location information. Therefore, the combination of PET and CT imaging can provide complementary advantages to achieve accurate early diagnosis of tumors. However, currently developed PET or CT imaging agents have only a single function. Here, we designed and constructed a self-assembled lipid nanocapsule encapsulated with iodixanol and labeled with self-chelated Cu-64 for precise PET/CT imaging of tiny lung tumor. The lipid nanocapsule self-assembled in water using LPPC-Ce6, a conjugate of chlorin e6 (Ce6) and lysophosphatidylcholine (LPPC), to form a bilayer vesicular structure. Cu-64 was embedded in the center of the tetrapyrrole ring of Ce6 by natural capture ability for Cu2+ ions. GLT21.T, the aptamer targeting lung cancer, was conjugated to the surface of the lipid nanocapsules. Iodixanol was loaded into the cavity of the lipid nanocapsule (Cu-64@LCI-apt). In the nanostructure, the loading of iodixanol was sufficiently high, and the specific activity could be flexibly adjusted according to imaging requirements. The prepared Cu-64@LC1-apt achieves excellent radiolabeling efficiency, stability and effective targeting of lung tumor. In an early orthotopic lung cancer model, Cu-64@LCI-apt demonstrated the capabilities of sensitive PET imaging and enhanced contrast CT imaging to enable efficient high-quality PTE/CT imaging of tiny orthotopic lung tumor with a diameter of 500 mu m. Cu-64@LCI-apt has great potential for early, sensitive, and accurate diagnosis of tumors through dual-mode PET/CT imaging.