Molecular Engineering of Glycoaptamer Dual-Target Radionuclide Probes for PET/CT Imaging of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is one of the most malignant cancer types, characterized by a lack of efficient diagnostic and treatment methods in clinical practice. The development of effective targeted diagnosis and treatment for TNBC has become an important research focus. Here, we report the first proof-of-concept evidence of a glycoaptamer dual-target radionuclide probe (GDRP) for positron emission tomography/computed tomography (PET/CT) imaging of TNBC. The GDRP was created through precise molecular engineering of the aptamer AS1411, combined with three mannose ligands. The GDRP exhibited significantly increased serum stability and a high affinity for TNBC cells through a dual targeting mode. The advantages of our developed GDRP were further demonstrated by its excellent <i>in vivo</i> PET/CT dynamic imaging performance, featuring a long imaging window and high spatiotemporal resolution. This flexible method allows for the preparation of glycosylated functional nucleic acid molecular probes with high serum stability and tumor specificity. We anticipate that this PET/CT molecular probe will expand the development of glycoaptamer-based radioactive drugs and provides molecular tools for the clinical diagnosis of TNBC.