Bench to Bedside: Albumin Binders for Improved Cancer Radioligand Therapies

Radioligand therapy (RLT) relies on the use of pharmacophores to selectively deliver ionization energy to cancers to exert its tumoricidal effects. Cancer cells that are not directly targeted by a radioconjugate remain susceptible to RLT because of the crossfire effect. This is significant given the inter- and intra-heterogeneity of tumors. In recent years, reversible albumin binders have been used as simple "add-ons" for radiopharmaceuticals to modify pharmacokinetics and to enhance therapeutic efficacy. In this Review, we discuss recent advances in albumin binder platforms used in RLT, with an emphasis on 4-(p-iodophenyl)butyric acid and Evans blue derivatives. We focus on four biological systems pertinent to oncology that utilize this class of compounds: folate receptor, integrin αvβ3, somatostatin receptor, and prostate-specific membrane antigen. Finally, we offer our perspectives on albumin binders for RLT, highlighting future areas of research that will help propel the technology further for clinical use.