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

将[Cu-64] Cu-二乙酰基-双（N4-甲基缩氨基硫脲）（^<64>Cu-ATSM）和氟-18 2-氟-2-脱氧葡萄糖（^<18>FDG）在四种不同来源的荷瘤小鼠（LLC 1、Meth-A、B16和colon 26）中的瘤内分布与增殖细胞（Ki 67）、血管（CD 34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（TdT）介导的dUTP缺口末端标记（TUNEL）方法）的免疫组织化学染色进行比较。在所有细胞系中，^<64>Cu-ATSM和^<18>FDG分布于肿瘤块的不同区域。免疫组织化学研究表明，高的<64>Cu-ASTM吸收区域是少血管的，由停滞在细胞周期中的肿瘤细胞组成，而高的<18>FGD吸收区域是多血管的，由增殖细胞组成。通过我们的研究，发现一个肿瘤包含两个不同特征的区域，这可以通过^<64>Cu-ATSM和^<18>FDG来区分。由于缺氧和细胞周期阻滞是降低肿瘤对放射和常规化疗敏感性的关键因素，因此肿瘤中具有这些特征的区域应作为主要靶点之一进行集中治疗。Cu-ATSM<64>可以描绘肿瘤中的缺氧和细胞周期停滞区域，可以为癌症治疗提供有价值的信息，以及作为内部放射治疗试剂直接治疗这些区域的可能性。

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.