Tc(V)- D M S的肿瘤定位机制:葡萄糖介导的酸中毒使肿瘤摄取对p H 敏感的 Tc(V)- D M S的靶/非靶比值增大

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目的: Tc(Ⅴ) D M S能够对多种肿瘤进行显像,但显像机制尚无定论。本研究拟观察葡萄糖介导的酸中毒肿瘤摄取 Tc(Ⅴ) D M S程度的影响,以证实肿瘤摄取该药时对p H 值的敏感性。方法:荷 Ehrlich 腹水癌细胞株的小鼠 15 只,肿瘤种植部位为大腿内侧肌肉内。以直接微电极法和组化伞形酮法测定肿瘤组织的 p H 值,以放射自显影法测定局部放射性强度,经 30% ~40% 葡萄糖预处理动物模型改变肿瘤组织的 p H 值。结果:血清测定表明,荷瘤小鼠的葡萄糖水平显著低于正常对照组。给予葡萄糖刺激动态测定,发现荷瘤小鼠组的上升幅度小、下降快,提示肿瘤处的葡萄糖代谢率增高,而直接微电极法与组化法证实肿瘤组织处的p H 值低于肌肉处;肿瘤处的 p H 值在葡萄糖预处理组与未处理组之间的差异达到 015~046。将 Tc(Ⅴ) D M S的摄取以百分数表示,未给予葡萄糖处理的肿瘤处与肌肉组织处每克分别为0243% ±0030% 和 0157% ±0068% ,二者比值为 177;给予葡萄糖 5g/kg 预处理组的肿瘤处的摄取值每克为 0362% ±0100% ,加大葡萄糖用量至6g/kg 时,该值上升至每克 0710% ±? Purpose: Tc(V)-DMS can image a variety of tumors, but the imaging mechanism is inconclusive. The purpose of this study was to observe the effect of Tc(V)-DMS on the uptake of glucose-mediated acidosis tumors, in order to confirm the sensitivity of the tumors to p H values ​​when taking the drug. METHODS: Fifteen mice bearing Ehrlich ascites carcinoma cell line were implanted in the inner thigh muscle. The p H value of tumor tissue was measured by direct microelectrode method and histochemical umbelliferone method. The local radioactive intensity was measured by autoradiography. The p H value of the tumor tissue was changed by a 30% to 40% glucose pretreated animal model. Results: Serum measurements showed that glucose levels in tumor-bearing mice were significantly lower than in normal controls. When glucose stimulation was measured dynamically, it was found that the tumor-bearing mice group had a small increase and a rapid decrease, suggesting an increase in the glucose metabolism rate at the tumor site. Direct microelectrode and histochemistry confirmed that the p H value at the tumor tissue was lower than that at the muscle site. The difference in p H values ​​between the glucose pretreatment group and the untreated group reached 015~046. The uptake of Tc(V)-DMS was expressed as a percentage, and 0.243% ± 0. 030% and 0. 157% ± 0. 068% per g of tumor and muscle tissue where glucose was not administered. The ratio between the two values ​​was 177; the uptake value of the tumor in the pretreatment group given glucose 5g/kg was 0362%±0100% per gram. When glucose was increased to 6g/kg, the value rose to Ke 0710% ±?
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