| 聂琦,刘璐,刘志勇,黄培林,兰兴昊,高海林,吴清华,孙晋,黄鹰.胶体32P-磷酸铬间质给药对犬累积损伤效应的研究[J].中华放射医学与防护杂志,2010,30(1):9-14 |
| 胶体32P-磷酸铬间质给药对犬累积损伤效应的研究 |
| Cumulative damage effect of 32P-colloidal chromic phosphate interstitial delivery on beagles |
| 投稿时间：2009-06-29 |
| DOI： |
| 中文关键词: 胶体32P-磷酸铬 间质 动物 安全性 |
| 英文关键词:32P-colloidal chromic phosphate Interstitial Experimental animal Security |
| 基金项目:国家863项目(2007AA02Z471) |
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| 摘要点击次数: 2921 |
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| 中文摘要: |
| 目的 探讨胶体32P-磷酸铬(32P-CP)在正常Beagle犬的肝叶或臀大肌行间质注射的安全性。方法 10只Beagle犬,随机分成间质给药不同剂量(185和370MBq)、不同部位(臀大肌和肝脏)及冷胶体对照5组(n＝2)。术后不同时间点称量体重,行血液生化学检查,ECT轫致辐射显像,组织形态学动态观察及连续测量体表、血液、尿液和粪便放射性计数率值。计量数据以均数±标准差(±s)表示,采用SPSS13.0软件进行统计分析。结果 给药后ECT示肝脏组全肝显影,放射性分布呈团块状不均匀,肌肉组局部放射性持续浓聚,肝脏未见显影。术后第4组犬体重进行性减少,45d时较术前减少2.7kg,余组体重增值均数依序为3.0、1.6、0.8和3.1kg。第4组血小板、红细胞术后有明显减少。分别于给药后23和45d死亡,死亡前谷草转氨酶和谷丙转氨酶均有急剧升高;其余组间血液和血生化学差异无统计学意义。术后体表分区测定以注射部位放射性计数率值为最高,其次为膀胱、脾。肝脏组血液峰时为5min,峰值分别为0.5×107/min和1.0×107/min;肌肉组持续在3×105/min左右。组织学表现肌肉组和肝脏185MBq组4周内有充血水肿改变,8周后组织结构恢复正常;肝脏370MBq组4周内部分肝细胞坏死,6周时见大量肝细胞气球样变,充血水肿明显,肝小叶结构不清。尿液、粪便中放射性计数率肌肉组峰时均数分别为13和12d,峰值为(42.0±3.3)×104/min和(29.6±4.5)×104/min;肝脏组峰时为5和9d,峰值为(49.0±10.2)×104/min和(28.5±7.1)×104/min。至30d肌肉组从尿液和粪便中累积排泄率为36.58%和10.62%,肝脏组为23.48%和8.76%。吸收剂量肝脏组肝脏为(30.6±2.3)、(55.6±4.4)Gy;肌肉组肌肉注射部位为(53.4±3.1)、(98.1±3.3)Gy,肝脏为(2.3±1.3)、(6.5±1.2)Gy。结论 Beagle犬肝脏间质注射794.39MBq/m2,肝脏吸收剂量为56Gy时有较强肝毒性及全身毒副作用,是其致死剂量。肌肉给药463.98～772.93MBq/m2是安全剂量范围。32P-CP间质给药是适用于治疗凡穿刺所能到达的乏血供及中等血供实体瘤的安全手段。 |
| 英文摘要: |
| Objective To explore the possibility and safety of 32P-colloidal chromic phosphate interstitial injection. Methods Ten Beagle dogs were randomly divided into 5 groups ( n =2) according to different doses (185 and 370 MBq), different sites (gluteus maximus and liver) and cold colloid as a control group. At different time-points after surgery, the weights of dogs were measured, and the blood and blood biochemical inspections were examined. ECT imaging was performed and histomorphology was observed dynamically. The radioactive counts of body surface for 90 days, blood for 12 weeks and urine and feces for 30 days were measured continuously. Measured data were expressed by mean ± standard error ( ±s) and SPSS 13.0 software was used for statistical analysis. Results ECT imaging demonstrated that the whole liver imaging was obtained although the radioactive distribution was uneven in liver groups, and the radioactivity concentrated continuously in the area of injection, but no liver imaging in muscle groups. Dogs in group 4 lost weight progressively and reduced by 2.7 kg till 45 d after operation. While the mean weight increments in the other groups were 3.0, 1.6, 0.8 and 3.1 kg in order. In group 4, PLT and RBC reduced obviously. Dogs died at 23 or 45 d. AST and ALT were elevated sharply before death. In the other groups, blood and blood biochemistry inspection showed there were no significant statistical differences. The highest radioactive counts after operation were obtained from the injection spot, while the urinary bladder and the spleen were followed. The peak of blood cpm in liver groups presented at 5 min.Peak values were 0.5×107/min and 1.0×107/min, respectively. The blood cpm in the muscle groups was always maintained at 3×105/min. Histology study showed the hyperemia dropsy changes in muscle groups and 185 MBq liver group in 4 weeks, while after 8 weeks the organizational structure restored normally. There were partial liver cells necrosis in 4 weeks, and the massive liver cells balloon type changes in 6 weeks, as well as obvious hyperemia dropsy and the hepatic lobe structure unclear in 370 MBq liver group. For the radioactive counts of urine and excrement, the peak appeared at 13 and 12 d respectively, and the peak values were (42.0±3.3)×104 and (29.6±4.5)×104/min in muscle groups, respectively ; while the peak appeared at 5 and 9 d, respectively and the peak values were (49.0±10.2)×104 and (28.5±7.1)×104/min in liver groups, respectively. Cumulative excretion ratios in urine and excrement were 36.58% and 10.62% in muscle groups, respectively and 23.48% and 8.76% in liver groups till 30 d, respectively. The liver absorbed doses were 30.6 and 55.6 Gy in liver groups, while those were 2.3 and 6.5 Gy in muscle groups. The maximus absorbed doses of gluteus were 53.4 and 98.1 Gy in muscle groups. Conclusions When 32P-colloidal chromic phosphate of 794.39 MBq/m2 was injected into the liver of Beagle, the liver absorbed dose was 56 Gy, which could be lethal dose for its strong liver toxicity and systemic side effects. Injection of 463.98-772.93 MBq/m2 in muscle of Beagle could be safe. 32P-colloidal chromic phosphate interstitial injection is secure to treat the solid tumors with poor and middle blood supply which could be reached by puncture. |
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