在腫瘤血管新生(angiogenesis)之過程中，內皮細胞形成新的微血管時，會表現細胞黏著分子（cell adhesion molecules），通稱為整合素（integrin）。惡性神經膠質瘤（glioblastoma multiforme）細胞生長期會大量表現一種稱為αvβ3之整合素（密度達(1.28±0.46)×105 receptors/cell）。αvβ3整合素已被充分證實可被細胞外基質中一特定胺基酸序列Arg-Gly-Asp（RGD）所辨識。本研究為藉此RGD專一標靶特性，製備一種主動標靶之放射免疫治療試劑131I- E[c(RGDyK)]2，並對具有高腫瘤血管新生表現之惡性神經膠質瘤動物模式進行放射免疫治療之療效評估。
方法：以iodogen方法將放射性核種I-131標誌於E[c(RGDyK)]2上。利用nanoSPECT/CT造影以及腫瘤組織切片試驗，確認於神經膠質瘤動物模式中，131I-E[c(RGDyK)]2能確實利用其主動標靶之特性達到長時間停留於腫瘤中。進一步以生物分佈試驗以及輻射劑量運算評估131I-E[c(RGDyK)]2之治療潛力。最後，於神經膠質瘤動物模式中，進行單次劑量及分次劑量131I-E[c(RGDyK)]2之放射免疫治療，同時以組織病理學分析確定131I-E[c(RGDyK)]2之放射治療結果。
結果：本實驗所合成之131I-E[c(RGDyK)]2，能於大鼠血清中達到90%以上之穩定度。於nanoSPECT/CT造影、放射自動顯影(autoradiography) 、活體外及活體內生物分佈試驗結果中，均能相互呼應並顯示出於神經膠質瘤腫瘤中，131I-E[c(RGDyK)]2之累積約為3 %ID/g (注射後30分鐘)、最高T/N (tumor to normal tissue ratio)值為8∼13出現於注射後24小時。於皮下神經膠質瘤動物模式之放射免疫治療試驗中，給予放射藥物治療之動物與未治療組呈現統計上之差異，腫瘤生長抑制之結果顯示於給藥後第十天分次劑量組別與單次劑量達到統計學上之差異。最後於免疫組織化學分析結果中，發現131I-E[c(RGDyK)]2能降低腫瘤細胞間之血管密度，顯示放射免疫治療之功效。
結論：本研究初步成功地呈現131I-E[c(RGDyK)]2於皮下神經膠質瘤動物模式之放射免疫治療效果，未來將進一步於原位惡性神經膠質瘤動物模式中探討惡性神經膠質瘤動物模式之抑制效果。

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