Preparation, radioiodination and in vitro evaluation of a nido-carborane-dextran conjugate, a potential residualizing label for tumor targeting proteins and peptides

Polysaccharides are not degradable by proteolytic enzymes in lysosomes and do not diffuse through cellular membranes. Thus, attached to an internalizing, targeting protein, such polysaccharide linkers, will remain intracellularly after protein degradation. They can be labeled with halogens and provide then a so called residualizing label. Such an approach improves tumor-to-non-tumor radioactivity ratio and, consequently, the results of radionuclide diagnostics and therapy. In this study we present a new approach to obtain a stable halogenation of the polysaccharide dextran using 7-(3-amino-propyl)-7,8-dicarba-nido-undecaborate (-) (ANC). Dextran T10 was partially oxidized by metaperiodate, and ANC was coupled to dextran by reductive amination. The conjugate was then labeled with I-125 using either Chloramine-T or lodoGen as oxidants. Labeling efficiency was 69-85%. Stability of the label was evaluated in rat liver homogenates. Under these conditions, the ANC-dextran conjugate was found to be more stable than labeled albumin, which was used as a control protein.