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    • 10. 发明申请
    • TRICARBONYL TECHNETIUM-99m OR RHENIUM-188 LABELED CYCLIC RGD DERIVATIVES, A PREPARATION METHOD THEREOF, AND A PHARMACEUTICAL COMPOSITION CONTAINING THE DERIVATIVES AS AN ACTIVE INGREDIENT FOR USE IN THE DIAGNOSIS OR TREATMENT OF ANGIOGENESIS-RELATED DISEASES
    • 三溴联苯技术-99m或RHENIUM-188标记循环RGD衍生物及其制备方法,以及含有衍生物作为活性成分的药物组合物用于诊断或治疗血管发生相关性疾病
    • US20130064766A1
    • 2013-03-14
    • US13699511
    • 2011-05-24
    • Byung Chul LeeSang Eun KimJi Sun KimByung Seok MoonJae Ho Jung
    • Byung Chul LeeSang Eun KimJi Sun KimByung Seok MoonJae Ho Jung
    • A61K51/08C07K1/13A61P9/00C07K7/64
    • A61K51/088A61K51/082C07D273/06C07D498/06C07D498/16C07K7/64G01N33/574G01N33/60
    • The present invention relates to tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives, a preparation method thereof, and a pharmaceutical composition containing the derivative as an active ingredient for use in the diagnosis or treatment (radiotherapy) of angiogenesis-related diseases. The tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives of the present invention has a high subnanomolar affinity to integrin αvβ3 (also called as a vitronectin receptor) that is activated in an angiogenic action induced by a tumor, reflects a high tumor image of the tricatvonyl technetium-99m labeled cyclic RGD derivative after initial intake in an animal in which cancer cells are transplanted, and acts exclusively upon cancer cells having selectively activated integrin αvβ3 because of a substantially low intake into the liver and intestines, compared to existing known radioactive isotope labeled cyclic RGD derivatives. These results show that the rhenium-188 labeled derivative, a therapeutic nuclide using the same precursor as used in the technetium-99m labeling, effectively inhibits the growth of a tumor and demonstrates therapeutic efficacy when administered via tail vein injection to an animal model bearing tumor, compared to a case where only saline has been injected, thereby making it useful as a medicine for the diagnosis or treatment of angiogenesis-related diseases.
    • 本发明涉及三羰基锝-99m或铼-188标记的环状RGD衍生物,其制备方法和含有该衍生物作为血管生成相关疾病的诊断或治疗(放射治疗)的有效成分的药物组合物。 本发明的三羰基锝-99m或铼-188标记的环状RGD衍生物在由肿瘤诱导的血管生成作用中被激活的整联蛋白αv&bgr 3(也称为玻连蛋白受体)具有高亚纳摩尔亲和力,反映了高 在移植了癌细胞的动物中,首先摄入三氯乙酰锝-99m标记的环状RGD衍生物的肿瘤图像,并且完全作用于具有选择性活化整联蛋白αv&bgr3的癌细胞,因为进入肝脏和肠的摄入量很低, 与现有已知的放射性同位素标记的环状RGD衍生物相比。 这些结果表明,使用与锝-99m标记中使用的相同前体的治疗性核素的铼-188标记的衍生物有效地抑制肿瘤的生长,并且当通过尾静脉注射施用于携带肿瘤的动物模型时显示出治疗功效 ,与仅注射盐水的情况相比,可以用作诊断或治疗血管发生相关疾病的药物。