In vitro and in vivo evaluations of a radioiodinated thymidine phosphorylase inhibitor as a tumor diagnostic agent for angiogenic enzyme imaging
In vitro and in vivo evaluations of a radioiodinated thymidine phosphorylase inhibitor as a tumor diagnostic agent for angiogenic enzyme imaging
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DOI：
10.1016/j.nucmedbio.2010.01.005
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发表时间：
2010-05-01
影响因子：
3.1
通讯作者：
Ohkura, Kazue
中科院分区：
文献类型：
--
作者：
Akizawa, Hiromichi;Zhao, Songji;Ohkura, Kazue
胸苷磷酸化酶（TP）的表达与血管生成、肿瘤侵袭性和肿瘤活化密切相关。抗肿瘤剂。我们评估了具有高TP抑制效能的放射性碘化5-碘-6-[（2-亚氨基咪唑烷基）甲基]尿嘧啶（[I-125]IIMU）作为SPECT靶向肿瘤TP表达的新型放射性示踪剂。方法：通过肿瘤细胞对放射性碘化TP抑制剂IIMU的体外吸收和体内生物分布研究来确定其特性。用计数法测定荷瘤小鼠体内示踪剂的分布及肿瘤对tp的特异性摄取程度。结果：高TP表达的A431细胞对放射性标记IIMU的体外摄取归因于放射性示踪剂与其靶酶即TP的结合。放射性示踪剂在A431荷瘤小鼠体内分布显示，注射后3小时，肿瘤/血液和肿瘤/肌肉活动摄取比分别为36和106。在使用低TP表达的肿瘤和TP阻断研究作为对照时，在这些研究中检测到少量TP特异性的放射性示踪剂积累。结论：根据放射性碘化IIMU与血管生成酶TP的结合，可以认为放射性IIMU可能适合作为肿瘤显像的SPECT示踪剂。(C) 2010爱思唯尔公司版权所有。
Introduction: The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis, tumor invasiveness and activation of. antitumor agents. We evaluated radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ([I-125]IIMU) having high TP-inhibitory potency as the new radiotracer for SPECT targeting of TP expression in tumors.Methods: The characteristics of the radioiodinated TP inhibitor IIMU were determined by evaluating the uptake by tumor cells in vitro and by biodistribution studies in vivo. The distribution of the radiotracer and the extent of TP-specific uptake by tumors were evaluated by a counting method in tumor-bearing mice.Results: The in vitro uptake of radiolabeled IIMU by A431 cells along with high TP expressions was attributed to the binding of the radiotracer to its target enzyme, i.e., TP. In vivo distribution of the radiotracer in A431 tumor-bearing mice revealed tumor/blood and tumor/muscle activity uptake ratios of 36 and 106, respectively, at 3 h after the radiotracer injection. On using low TP-expressing tumors and TP blocking studies as controls, minor TP-specific accumulation of the radiotracer was detected in these studies.Conclusion: According to the binding of radioiodinated IIMU to the angiogenic enzyme TP, it can be concluded that radioiodinated IIMU might be suitable as a SPECT tracer for tumor imaging. (C) 2010 Elsevier Inc. All rights reserved.