Bispecific Radioligands (BRLs): Two Is Better Than One

Inter- or intra-tumor heterogeneity refers to the genetic, epigenetic, and phenotypic variability that characterizes tumor cells. Regardless of its nature, this complexity represents a great challenge for diagnosis and treatment, since cells with different characteristics may respond differently to therapies, resulting in drug resistance and/or relapses. Furthermore, it has emerged that this heterogeneity can change over time or following a stimulus, such as a treatment. Molecular imaging is an essential tool in oncology. By enabling the identification of specific metabolic or receptor alterations of tumor cells, it provides a more accurate diagnosis, prognosis, and allows personalizing treatments. To date, addressing these challenges may be crucial for accurate diagnosis and therapeutic choice. In recent years, the design, synthesis, and characterization of bispecific radioligands (BRLs) with dual targeting capacity has emerged. In this review, we discuss the in vitro and in vivo studies of this new class of radiopharmaceuticals conducted so far, while assessing their potential advantages over traditional single-target radiopharmaceuticals.