靶向mtDNA平行型G-四链体的多肽PET探针在实体肿瘤成像的应用

G-quadruplexes are widely distributed in human genes and exhibit upregulation in cancer cells. While numerous studies explore G-quadruplexes as potential drug targets, research focused on utilizing DNA G-quadruplexes for specific detection and visualization of solid tumors in vivo remains relatively limited. Here, we engineered a PET peptide probe [18F]AlF-NOTA-RHAU18 derived from DEAH-box helicase RHAU. The probe was designed to detect and visualize solid tumors in vivo using the radionuclide fluoride-18 by specific detection of parallel G-quadruplex DNA. The specific binding and affinity of the peptide to nucleic acids was evaluated in vitro. In cellular imaging studies, we used FITC-labelled RHAU18 for imaging and were surprised to find that the peptide preferentially binds to mitochondrial G-quadruplexes. In living homozygous mice, enrichment of the [18F]AlF-NOTA-RHAU18 peptide probe in the tumor was observed by micro-PET. Our work may provide new avenues for the detection of G-quadruplexes in vivo and the development of innovative cancer diagnostic tools.