Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Nucl Med Biol. 2010 May;37(4):427-32. doi: 10.1016/j.nucmedbio.2010.01.005. Epub 2010 Apr 8.
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 ([(125)I]IIMU) having high TP-inhibitory potency as the new radiotracer for SPECT targeting of TP expression in tumors.
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.
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.
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.
胸苷磷酸化酶（TP）的表达与血管生成、肿瘤侵袭性和抗肿瘤药物的激活密切相关。我们评估了具有高 TP 抑制活性的放射性碘标记 5-碘-6-[[2-亚氨基咪唑烷-1-基]甲基]尿嘧啶（[(125)I]IIMU）作为 SPECT 靶向肿瘤中 TP 表达的新型放射性示踪剂。
通过评估肿瘤细胞体外摄取和体内生物分布研究，确定放射性碘标记 TP 抑制剂 IIMU 的特性。通过在荷瘤小鼠中进行计数方法评估放射性示踪剂的分布和肿瘤对 TP 特异性摄取的程度。
A431 细胞对标记的 IIMU 的体外摄取以及高 TP 表达归因于放射性示踪剂与其靶酶，即 TP 的结合。在 A431 荷瘤小鼠中放射性示踪剂的体内分布显示，在放射性示踪剂注射后 3 小时，肿瘤/血液和肿瘤/肌肉摄取比值分别为 36 和 106。在使用低 TP 表达肿瘤和 TP 阻断研究作为对照的情况下，在这些研究中检测到放射性示踪剂的少量 TP 特异性积累。
根据放射性碘标记的 IIMU 与血管生成酶 TP 的结合，可以得出结论，放射性碘标记的 IIMU 可能适合作为肿瘤成像的 SPECT 示踪剂。
