Tanaka Takeshi, Furukawa Takako, Fujieda Shigeharu, Kasamatsu Shingo, Yonekura Yoshiharu, Fujibayashi Yasuhisa
Department of Otorhinolaryngology, University of Fukui, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.
Nucl Med Biol. 2006 Aug;33(6):743-50. doi: 10.1016/j.nucmedbio.2006.05.005. Epub 2006 Jul 18.
We studied the regional characteristics within tumor masses using PET tracers and immunohistochemical methods.
The intratumoral distribution of (64)Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([(64)Cu]Cu-ATSM) and [(18)F] 2-fluoro-2-deoxyglucose ((18)F]FDG) in mice with tumors of four different origins (LLC1, Meth-A, B16 and colon26) was compared with the immunohistochemical staining of proliferating cells (Ki67), blood vessels (CD34 or von Willebrand factor), and apoptotic cells (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling method).
With all cell lines, [(64)Cu]Cu-ATSM and [(18)F]FDG were distributed with different gradation in the tumor mass. The immunohistochemical study demonstrated that the high [(64)Cu]Cu-ATSM uptake regions were hypovascular and consisted of tumor cells arrested in the cell cycle, whereas the high [(18)F]FDG uptake regions were hypervascular and consisted of proliferating cells.
In our study, it was revealed that one tumor mass contained two regions with different characteristics, which could be distinguished by [(64)Cu]Cu-ATSM and [(18)F]FDG. Because hypoxia and cell cycle arrest are critical factors to reduce tumor sensitivity to radiation and conventional chemotherapy, regions with such characteristics should be treated intensively as one of the primary targets. [(64)Cu]Cu-ATSM, which can delineate hypoxic and cell cycle-arrested regions in tumors, may provide valuable information for cancer treatment as well as possibly for treating such regions directly as an internal radiotherapy reagent.
我们使用正电子发射断层显像（PET）示踪剂和免疫组化方法研究了肿瘤块内的区域特征。
比较了（64）铜 - 双乙酰 - 双（N4 - 甲基硫代半卡巴腙）（[(64)Cu]Cu - ATSM）和[(18)F]2 - 氟 - 2 - 脱氧葡萄糖（[(18)F]FDG）在四种不同起源肿瘤（LLC1、Meth - A、B16和结肠26）小鼠肿瘤内的分布情况，并与增殖细胞（Ki67）、血管（CD34或血管性血友病因子）和凋亡细胞（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法）的免疫组化染色结果进行对比。
对于所有细胞系，[(64)Cu]Cu - ATSM和[(18)F]FDG在肿瘤块内呈不同程度分布。免疫组化研究表明，[(64)Cu]Cu - ATSM摄取高的区域血管较少，由细胞周期停滞的肿瘤细胞组成，而[(18)F]FDG摄取高的区域血管丰富，由增殖细胞组成。
在我们的研究中发现，一个肿瘤块包含两个具有不同特征的区域，可通过[(64)Cu]Cu - ATSM和[(18)F]FDG区分。由于缺氧和细胞周期停滞是降低肿瘤对放疗和传统化疗敏感性的关键因素，具有此类特征的区域应作为主要靶点之一进行强化治疗。[(64)Cu]Cu - ATSM能够描绘肿瘤内的缺氧和细胞周期停滞区域，可为癌症治疗提供有价值的信息，也可能作为一种内放射治疗试剂直接用于治疗此类区域。
