Basic studies on positive imaging of hypoxic tissue in malignant tumor

恶性肿瘤大多含有缺氧组织，这对放射治疗有登记作用。我们进行了基础研究，积极成像使用放射性示踪剂，积累到缺氧细胞。1-用铬胺-T法分别用I-125或I-123标记了一种新的含酚基的2-硝基咪唑衍生物（N-（4 '-羟基苯基）乙酰胺-2-硝基咪唑）。观察到与氧浓度降低相关的放射性细胞蓄积较高。荷瘤小鼠的组织分布研究显示，肿瘤中的放射性显著保留，而正常需氧组织快速吸收并清除，与血液清除平行。放射自显影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较治疗前降低。磁共振波谱也显示放射治疗后Pi/b-NTP比值和pH值的改善，这表明肿瘤组织的复氧。我们的初步研究表明，与I-123标记的硝基咪唑衍生物的成像可能是有希望的恶性肿瘤的阳性检测和潜在的预测肿瘤对放射治疗的反应和/或监测在早期阶段的治疗效果。

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.