131^I-cRGD环肽对荷黑色素瘤小鼠的靶向治疗作用

An experimental study on targeted therapy of radioiodinated cyclic cRGD peptide on melanoma bearing mice

目的用131^I标记环精氨酸-甘氨酸-天冬氨酸（cRGD）肽，探讨131^I-cRGD对荷黑色素瘤小鼠模型瘤体生长的双重抑制作用。方法应用氯胺T法对cRGD进行131^I标记。建立荷黑色素瘤B16株小鼠模型，将20只荷瘤小鼠按完全随机化法分为4组，每组5只，即实验（131^I-cRGD）组、cRGD对照组、131^I-甘氨酸-甘氨酸-甘氨酸（cGGG）对照组和空白对照（PBS）组，分别经尾静脉注射相应药物，观察各组荷瘤小鼠肿瘤体积和质量的变化，利用单因素方差分析比较各组之间的差异。结果131^I-cRGD的标记率和放化纯分别达到（89．14±4．57）％及（99．14±0．72）％。治疗第21天时，各组与PBS组肿瘤体积相比，抑瘤率分别为64．92％（131^I-cRGD组）、37．70％（cRGD组）及24．78％（131^I-cGGG组）；治疗第28天时，处死各组小鼠，其瘤质量（舍治疗第21～28天自然死亡的4只小鼠）分别为131^I-cRGD组（6．48±5．19）g、cRGD组（10．81±6．25）g、131^I-cGGG组（14．21±5．91）g、PBS组（18．88±7．59）g（F=3．479，P〈0．05），131^I-cRGD组与PBS组之间差异有统计学意义（t=3．12，P〈0．05）。各组与PBS组肿瘤质量相比，抑瘤率分别为65．72％（131^I-cRGD组）、42．76％（cRGD组）及24．77％（131^I-cGGG组）。治疗第28天时，各组小鼠净体质量（净体质量=小鼠体质量-瘤质量，含治疗第21～28天死亡的4只小鼠）分别为（29．12±8．66）g（131^I-cRGD组）、（25．89±6．49）g（cRGD组）、（24．29±2．97）g（131^I-cGGG组）、（20．92±5．95）g（PBS组），差异无统计学意义（F=1．444，P〉0．05）。结论131^I-cRGD能抑制荷黑色素瘤小鼠肿瘤的生长，对黑色素瘤治疗具有潜在的价值。

Objective Ectogenic Arg-Gly-Asp （RGD） peptide can bind to integrin α2β3 receptor on the cell membrane of tumor cells and neovasculature endothelial cells to prevent tumor growth and metastasis but was less potent than cRGD. The aim of this study was to further understand the inhibitory effect of cRGD labeled with 131^I in melanoma bearing mice. Methods cRGD peptide was labeled with 131^I by Ch-T method under the optimum labeling conditions. Twenty mice were randomly （complete randomization） divided into four groups, five for each group. There were experimental group （131^I-cRGD） , cRGD control group, 131^I-Gly-Gly-Gly （eGGG） control group and phosphate buffered saline （PBS） control group. All mice were injected through tail vein. Tumor volume, weight and net weight （ net weight = weight - the weight of the tumor） were measured for all and compared by one-way ANOVA. Results The labeling efficiency and the radiochemical purity of 131^I-cRGD peptide were （89.14 ±4.57 ）% and （99.14 ± 0.72）% respectively. Compared with the PBS group at 21st day, the tumor inhibitory rates were 64.92% for 131^I- cRGD group, 37.70% for cRGD group, and 24.78% for 131^I-cGGG group respectively. When sacrificed at 28th day, the weight was （6.48 ± 5.19） g for 131^I-cRGD group, （10.81 ± 6.25） g for cRGD group, （ 14. 21 ± 5.91 ） g for 131^I-cGGG group, and （ 18.88 ± 7.59 ） g for PBS group （ F = 3. 479, P 〈 0.05 ）. Significant difference was observed between 131^I-cRGD group and PBS group （ t = 3. 12, P 〈 0.05 ）. Compared with the PBS group at the end of treatment, the tumor inhibitory rates were 65.72% for 131^I-cRGD group, 42.76% for cRGD group, and 24.77% for 131^I-cGGG group respectively and with net weight of （29.12 ± 8.66） g for 131^I-cRGD group, （25.89 ± 6.49 ） g for cRGD group, （24.29 ± 2.97 ） g for 131^I- cGGG group, and （20.92 ± 5.95 ） g for PBS group （ F = 1. 444, P 〉 0.05 ）. Conclusion 131^I-cRGD could effectively inhibit tumor growth in melanoma bearing mice and might be of potential in treating melanoma in the future.