부산대학교 도서관

Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide–drug conjugates (PDCs) that target tumor-specific receptors such as integrin αvβ6are emerging as powerful tools to overcome these challenges. The development of an integrin αvβ6-selective PDC was achieved by combining the therapeutic efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity of the αvβ6-binding peptide (αvβ6-BP) and with the ability of positron emission tomography (PET) imaging by copper-64. The [64Cu]PDC-1was produced efficiently and in high purity. The PDC exhibited high human serum stability, integrin αvβ6-selective internalization, cell binding, and cytotoxicity. Integrin αvβ6-selective tumor accumulation of the [64Cu]PDC-1was visualized with PET-imaging and corroborated by biodistribution, and [64Cu]PDC-1showed promising in vivo pharmacokinetics. The [natCu]PDC-1treatment resulted in prolonged survival of mice bearing αvβ6(+) tumors (median survival: 77 days, vs αvβ6(−) tumor group 49 days, and all other control groups 37 days).