BLEDTA: tumor localization by a bleomycin analog containing a metal-chelating group

Abstract

Two different Co(III) complexes of the antitumor antibiotic bleomycin were prepared, and their in vivo distribution in mice was investigated. The more thermodynamically stable of the Co(III)-bleomycin complexes was modified by reaction with the bifunctional chelating agent EDTA, 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 1 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.