‡Affiliated Ruikang Hospital of Guangxi University of TCM, Nanning, Guangxi 530011, People's Republic of China.
⊥School of Physics, Beijing Institute of Technology, Beijing 100081, People's Republic of China.
ACS Nano. 2015 May 26;9(5):4976-86. doi: 10.1021/nn507130k. Epub 2015 May 1.
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, (64)Cu 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 (64)Cu. In this study, we have developed ultrasmall chelator-free radioactive [(64)Cu]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)Cu]CuNC@BSA-LHRH. The prepared [(64)Cu]Cu nanoclusters showed high radiolabeling stability, ultrasmall size, and rapid deposition and diffusion into tumor, as well as predominantly renal clearance. [(64)Cu]CuNC@BSA-LHRH showed 4 times higher tumor uptake compared with that of [(64)Cu]CuNC@BSA by analyzing the (64)Cu radioactivity of tissues via gamma counting. The PET imaging using [(64)Cu]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.
正电子发射断层扫描（PET）成像因其更高的灵敏度、时间分辨率和无限的组织穿透能力而受到特别关注。因此，开发针对特定分子的示踪剂对于开发和应用临床相关的 PET 程序至关重要。然而，（64）Cu 作为一种 PET 成像剂通常通过大环螯合剂引入生物材料中，这可能由于（64）Cu 的脱离和转螯合而导致 PET 成像结果的误判。在这项研究中，我们使用牛血清白蛋白（BSA）作为支架，开发了超小的无螯合剂放射性[（64）Cu]Cu 纳米团簇，用于在原位肺癌模型中的 PET 成像。我们预先将肿瘤靶肽促黄体激素释放激素（LHRH）缀合到 BSA 分子上，以制备[（64）Cu]CuNC@BSA-LHRH。所制备的[（64）Cu]Cu 纳米团簇表现出高放射性标记稳定性、超小尺寸、快速沉积和扩散到肿瘤中，以及主要的肾清除。通过组织伽马计数分析组织中的（64）Cu 放射性，与[（64）Cu]CuNC@BSA 相比，[（64）Cu]CuNC@BSA-LHRH 的肿瘤摄取量高 4 倍。使用[（64）Cu]Cu 纳米团簇作为示踪剂的 PET 成像显示，与近红外荧光成像相比，对体内原位肺癌的成像具有更高的灵敏度、准确性和更深的穿透能力。这些纳米团簇为 PET 分子成像提供了生物医学研究工具。
