Bench to Bedside: Albumin Binders for Improved Cancer Radioligand Therapies

• Published in: Bioconjugate chemistry 2019-03, Vol.30 (3), p.487-502
• Main Authors: Lau, Joseph, Jacobson, Orit, Niu, Gang, Lin, Kuo-Shyan, Bénard, François, Chen, Xiaoyuan
• Format: Article
• Language: English
• Subjects: Albumin; Antigens; Binders; Butyric acid; Cancer; Folic acid; Heterogeneity; Ionization; Oncology; Pharmacokinetics; Pharmacology; PharmacoPhores; Prostate; Somatostatin; Tumors
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.8b00919

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.