DeRiemer L H, Meares C F, Goodwin D A, Diamanti C I
J Med Chem. 1979 Sep;22(9):1019-23. doi: 10.1021/jm00195a001.
Two different Co(III) complexes of the antitumor antibiotic bleomycin have been prepared, and their in vivo distribution in mice has been investigated. The more thermodynamically stable of the Co(III)-bleomycin complexes has been modified by reaction with the bifunctional chelating agent 1-(p-bromoacetamidophenyl)ethylenedinitrilotetraacetic acid, to give a bleomycin derivative (BLEDTA) containing a powerful metal-chelating group. BLEDTA was radiolabeled with 111In(III) and its in vivo distribution in mice was examined. The potential of 111In-labeled BLEDTA as a tumor-visualizing agent was also investigated in humans with biopsy-proven cancers, predominantly (70%) squamous carcinoma of the head and neck. All of the 29 patients studied had at least one clinically proven site of the disease visualized with 111In-BLEDTA. These clinical results are significantly better than results we obtained in a comparable group of patients using directly labeled 111In-bleomycin and are similar to those reported by Nouel for 57Co-bleomycin [GANN Monogr. Cancer Res., 19, 301 (1976)].
制备了抗肿瘤抗生素博来霉素的两种不同的钴（III）配合物，并研究了它们在小鼠体内的分布。通过与双功能螯合剂1-（对溴乙酰氨基苯基）乙二胺四乙酸反应，对热力学更稳定的钴（III）-博来霉素配合物进行了修饰，得到了一种含有强大金属螯合基团的博来霉素衍生物（BLEDTA）。用铟（III）-111对BLEDTA进行放射性标记，并检测其在小鼠体内的分布。还在经活检证实患有癌症（主要为70%的头颈部鳞状癌）的人类患者中研究了铟（III）-111标记的BLEDTA作为肿瘤显像剂的潜力。所研究的29例患者中，所有患者至少有一个经临床证实的病灶能用铟（III）-111-BLEDTA显像。这些临床结果明显优于我们在一组使用直接标记的铟（III）-111-博来霉素的可比患者中获得的结果，并且与Nouel报道的57钴-博来霉素的结果相似[《癌症研究专论》，19，301（1976）]。
