Ultrasmall [64Cu] Cu Nanoclusters for Targeting Orthotopic Lung Tumors Using Accurate Positron Emission Tomography Imaging
Ultrasmall [64Cu] Cu Nanoclusters for Targeting Orthotopic Lung Tumors Using Accurate Positron Emission Tomography Imaging
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DOI：
10.1021/nn507130k
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发表时间：
2015-05-01
期刊：
影响因子：
17.1
通讯作者：
Gao, Xueyun
中科院分区：
文献类型：
--
作者：
Gao, Fuping;Cai, Pengju;Gao, Xueyun
正电子发射断层扫描（PET）成像由于其更高的灵敏度，时间分辨率和无限的组织穿透性而受到特别关注。因此，靶向特定分子的示踪剂的开发对于临床相关PET程序的开发和利用至关重要。然而，作为PET显像剂的Cu-64通常通过大环螯合剂引入到生物材料中，这可能导致由于Cu-64的脱离和转移螯合而导致PET成像结果的误解。在这项研究中，我们使用牛血清白蛋白（BSA）作为原位肺癌模型PET成像的支架，开发了超小的无螯合剂的放射性[Cu-64]Cu纳米团簇。我们将肿瘤靶肽促黄体激素释放激素（LHRH）预偶联到BSA分子上，制备了[（64）Ct]Cu-NC@BSA-LHRH。制备的[Cu-64]Cu纳米团簇显示出高的放射性标记稳定性、超小的尺寸、快速沉积和扩散到肿瘤中以及主要的肾清除。通过γ计数分析组织的Cu-64放射性，与[Cu-64]Cu-NC@BSA相比，[Cu-64] Cu-NC@BSA-LHRH显示出高4倍的肿瘤摄取。与近红外荧光成像相比，使用[Cu-64]Cu纳米团簇作为示踪剂的PET成像显示出体内原位肺癌的更灵敏、更准确和更深的穿透成像。纳米团簇为PET分子成像提供了生物医学研究工具。
Positron emission tomography (PET) imaging has received special attention owing to its higher sensitivity, temporal resolution, and unlimited tissue penetration. The development of tracers that target specific molecules is therefore essential for the development and utility of clinically relevant PET procedures. However, Cu-64 as a PET imaging agent generally has been introduced into biomaterials through macrocyclic chelators, which may lead to the misinterpretation of PET imaging results due to the detachment and transchelation of Cu-64. In this study, we have developed ultrasmall chelator-free radioactive [Cu-64]Cu nanoclusters using bovine serum albumin (BSA) as a scaffold for PET imaging in an orthotopic lung cancer model. We preconjugated the tumor target peptide luteinizing hormone releasing hormone (LHRH) to BSA molecules to prepare [(64)Ct]Cu-NC@BSA-LHRH. The prepared [Cu-64]Cu nanoclusters showed high radiolabeling stability, ultrasmall size, and rapid deposition and diffusion into tumor, as well as predominantly renal clearance. [Cu-64]Cu-NC@BSA-LHRH showed 4 times higher tumor uptake compared with that of [Cu-64]Cu-NC@BSA by analyzing the Cu-64 radioactivity of tissues via gamma counting. The PET imaging using [Cu-64]Cu nanoclusters as tracers showed more sensitive, accurate, and deep penetration imaging of orthotopic lung cancer in vivo compared with near-infrared fluorescence imaging. The nanoclusters provide biomedical research tools for PET molecular imaging.