BLEDTA: Tumor localization by a bleomycin analogue containing a metal-chelating group

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)].