| 邵国强,杨瑞,梁凯,姚晓晨,崔璨,王峰,王自正.99Tcm-3P4-RGD2 microSPECT/CT显像评价抗新生血管治疗肿瘤疗效价值的实验研究[J].中华放射医学与防护杂志,2017,37(1):12-18 |
| 99Tcm-3P4-RGD2 microSPECT/CT显像评价抗新生血管治疗肿瘤疗效价值的实验研究 |
| Study on 99Tcm-3P4-RGD2 microSPECT/CT imaging to anti-angiogensis therapeutic effect |
| 投稿时间：2015-06-08 |
| DOI：10.3760/cma.j.issn.0254-5098.2017.01.003 |
| 中文关键词: microSPECT/CT显像 脑胶质瘤 整合素αvβ3 抗新生血管治疗 |
| 英文关键词:MicroSPECT/CT imaging Quantitive analysis Integrin αvβ3 Anti-angiogensis therapy |
| 基金项目:国家自然科学基金（81301247）；江苏省自然科学基金（BK20130082） |
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| 中文摘要: |
| 目的探讨整合素αvβ3受体靶向microSPECT/CT显像在抗新生血管治疗肿瘤效果中的应用价值。方法构建荷人脑胶质瘤（U87MG）和荷人前列腺癌（PC-3）裸鼠模型。在肿瘤直径为6.0~7.0 mm时，分别给予Avastin治疗，并以生理盐水为对照组，在Avastin给药前1 d、给药后3、5、10和15 d，分别行99Tcm-3P4-RGD2 microSPECT/CT显像，测定肿瘤体积和放射性百分注射剂量率（% ID和% ID/g）摄取。监测荷瘤鼠一般情况，按照随机数字表法，在每个显像时间点取1只处死，进行病理学检查。结果 U87MG治疗组肿瘤体积在治疗后10 d明显小于U87MG对照组（t=5.81，P<0.05），差异有统计学意义，PC-3治疗组与PC-3对照组肿瘤体积差异无统计学意义（P>0.05）；U87MG治疗组肿瘤对99Tcm-3P4-RGD2摄取（% ID/g）在治疗前高于PC-3（t=10.48，P<0.05），给药后3 d低于U87MG对照组（t=3.26，P<0.05），且随着治疗进行逐渐减少，PC-3治疗组和对照组肿瘤摄取（% ID/g）均较低。病理结果显示，U87MG治疗组整合素β3表达降低以新生血管内皮为主，肿瘤细胞呈缓慢降低，U87MG肿瘤摄取（% ID/g）与整合素β3表达呈线性相关y=0.499 1x-0.243 8（R2=0.811 7）。结论Avastin治疗脑胶质瘤早期表现为新生血管整合素受体β3表达显著降低，99Tcm-3P4-RGD2 microSPECT/CT显像预期可作为脑胶质瘤抗新生血管治疗疗效早期评价的无创性手段。 |
| 英文摘要: |
| Objective To investigate the value of integrin αvβ3 targeted microSPECT/CT imaging with 99Tcm-3P4-RGD2 as a radiotracer in tumor anti-angiogenesis therapy.Methods Animal models bearing glioma and prostate cancer xenografts were established by subcutaneously injecting tumor cells U87MG and PC-3 in nude mice. Anti-angiogensis therapy with Avastin was administered via intraperitoneal injection when the tumor diameter reached 6 to 7 mm while saline was served as control group. MicroSPECT/CT imaging was performed with 99Tcm-3P4-RGD2 as radiotracer one day before and 3, 5, 10, 15 days after Avastin administration. Tumor volume and tumor uptake of 99Tcm-3P4-RGD2, expressed as percentage of injected dose (%ID) or%ID per gram (%ID/g) were measured and calculated based on microSPECT/CT. Mice basic condition was monitored and tumor xenograft was harvested in one tumor bearing nude mouse after its sacrifice at each imaging time point. Results Tumor volume of U87MG glioma in the administration group was significantly smaller than that of non-administration control group at 10 d after Avastin adminstration (t=5.81, P<0.05), while no significance was observed between the administration group and its control group of PC-3 tumor (P>0.05). The uptake of 99Tcm-3P4-RGD2 (%ID/g) in U87MG group was higher than that in PC-3 group before Avastin administration (t=10.48, P<0.05), and it decreased to a value less than control (t=3.26, P<0.05) at 3 d after Avastin administration and continually reduced at longer time after administration. PC-3 tumor had less uptake of 99Tcm-3P4-RGD2 in both Avastin administration group and its control group. The pathologic results revealed on that the decrease of tumor integrin β3 expression in U87MG treatment group was mainly on the endothelial cells of the neovessel. Linear relationship was verified between tumor uptake (%ID/g) and integrin β3 expression (y=0.499 1x-0.243 8, R2=0.811 7). Conclusions Complete inhibition of integrin is demonstrated early after Avastin administration. 99Tcm-3P4-RGD2 microSPECT/CT imaging, assessing the expression level of integrin αvβ3 level by quantification of tumor uptake of 99Tcm-3P4-RGD2, is probably an important method to reflect the early therapeutic effect of tumor anti-angiogensis. |
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