Basic studies on positive imaging of hypoxic tissue in malignant tumor

恶性肿瘤大多含有缺氧组织，这对放射治疗是有效的。我们使用放射性示踪剂对缺氧细胞进行了阳性成像的基础研究。1- (N-（4′-羟基苯基1）乙酰胺-2-硝基咪唑是一种含有苯酚残留物的新型2-硝基咪唑衍生物，采用常规的氯胺- t法用I-125或I-123标记。观察到与氧浓度降低有关的较高的细胞放射性积累。荷瘤小鼠的组织分布研究表明，放射性物质在肿瘤中有明显的保留，而正常的有氧组织在血液清除的同时迅速吸收和清除。放射自显像显示肿瘤内放射性不规则分布，与C-14标记的2-脱氧葡萄糖相似。放射治疗后，肿瘤摄取低于治疗前。MR谱还显示放射治疗后Pi/b-NTP比和pH值有所改善，提示肿瘤组织再氧化。我们的初步研究表明，使用I-123标记的硝基咪唑衍生物进行成像可能有助于恶性肿瘤的阳性检测，并可能在早期预测肿瘤对放射治疗的反应和/或监测治疗效果。

Malignant tumors mostly contain hypoxic tissue, which is registant to radiation therapy. We performed the basic studies on positive imaging using a radiotracer which accumulates to hypoxic cells. 1- (N- (4'-hydroxy-pheny1) acetamide-2-nitroimidazole, a new 2-nitroimidazole derivative including a phenol residue was labeled with I-125 or I-123 by the conventional chrolamine-T method. Higher cell accumulation of radioactivity was observed in relation to decreased oxygen concentrations. Tissue distribution study in tumor bearing mice showed significant retention of radioactovity in the tumors, while, normal aerobic tissues rapidly uptook and cleared parallel to blood clearance. Autoradiography imaged irregular distribution of radioactivity in the tumor, that was similar to that of C-14 labeled 2-deoxyglucose. After radiation therapy, tumor uptake was lower than that before therapy. MR spectroscopy also showed improved Pi/b-NTP ratio and pH values after radiation therapy, that suggested reoxygenation of tumor tissue. Our preliminary studies indicate that imaging with I-123 labeled nitroimidazole derivatives may be promise for positive detection of malignant tumors and potentially in predicting tumor response to radiation therapy and/or monitoring the therapeutic effect at the earlier phase.