Current State of Radiolabeled Heterobivalent Peptidic Ligands in Tumor Imaging and Therapy

Over the past few years, an approach emerged that combines different receptor-specific peptide radioligands able to bind different target structures on tumor cells concomitantly or separately. The reason for the growing interest in this special field of radiopharmaceutical development is rooted in the fact that bispecific peptide heterodimers can exhibit a strongly increased target cell avidity and specificity compared to their corresponding monospecific counterparts by being able to bind to two different target structures that are overexpressed on the cell surface of several malignancies. This increase of avidity is most pronounced in the case of concomitant binding of both peptides to their respective targets but is also observed in cases of heterogeneously expressed receptors within a tumor entity. Furthermore, the application of a radiolabeled heterobivalent agent can solve the ubiquitous problem of limited tumor visualization sensitivity caused by differential receptor expression on different tumor lesions. In this article, the concept of heterobivalent targeting and the general advantages of using radiolabeled bispecific peptidic ligands for tumor imaging or therapy as well as the influence of molecular design and the receptors on the tumor cell surface are explained, and an overview is given of the radiolabeled heterobivalent peptides described thus far.