Research on a new internal radiation therapy agent targeting for hypoxic tumors.

[铜-]铜-二乙酰-双(N4-甲基氨基硫脲)和氟-18-氟-2-脱氧葡萄糖(^&lt；18&gt；脱氧葡萄糖)在4种不同来源的荷瘤小鼠体内的分布与增殖细胞(Ki67)、血管(CD34或血管性血友病因子(VWF))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)的免疫组织化学染色进行了比较。所有的细胞系均分布在肿瘤的不同部位，如、铜-ATSM和FDG。免疫组织化学结果显示，高摄取区血管密度低，由细胞周期阻滞的肿瘤细胞组成；高摄取区血管丰富，由增殖的细胞组成。通过我们的研究发现，一个肿瘤包含两个不同特征的区域，可以通过^&lt；&gt；铜-ATSM和^&lt；18&gt；FDG来区分。由于低氧和细胞周期停滞是降低肿瘤对放疗和常规化疗敏感性的关键因素，因此肿瘤中具有这两个特征的区域应作为主要靶点之一进行强化治疗。铜-硫代巴比妥酸盐法可显示肿瘤内缺氧和细胞周期停滞区域，为肿瘤治疗提供有价值的信息，并为直接作为内照射试剂治疗此类区域提供有价值的信息。

Intratumoral distribution of [Cu-64]Cu-diacetyl-bis (N4-methylthiosemicarbazone) (^<64>Cu-ATSM) and fluorine-18 2-fluoro-2-deoxyglucose (^<18>FDG) in mice bearing tumors of four different origins, LLC1, Meth-A, B16 and colon26, were compared to the immunohistochemical staining for proliferating cells (Ki67), blood vessels (CD34 or von Willebrand Factor(vWF)) and apoptotic cells (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method). With all the cell lines, ^<64>Cu-ATSM and ^<18>FDG were distributed to different regions of the tumor mass. The immunohistochemical study demonstrated that the high ^<64>Cu-ASTM uptake regions were hypovascular and consisted of tumor cells arrested in cell cycle, while the high ^<18>FGD uptake regions were hypervascular and consisted of proliferating cells. Through our study, it was revealed that one tumor mass contains two regions of different characteristics, which can be distinguished by ^<64>Cu-ATSM and ^<18>FDG. Since hypoxia and cell cycle arrest are critical factors to reduce the sensitivity of tumor to radiation and conventional chemotherapy, regions with such characteristics in tumor should be treated intensively as one of the primary targets. ^<64>Cu-ATSM which can delineate hypoxic and cell cycle arrested regions in tumors can provide valuable information for cancer treatment as well as the possibility to treat such regions directly as an internal radiotherapy reagent.