Gallium-68LabeledCyclic Glycopeptides for LiverFunction Imaging

作者：Lixia Feng, Zhitao Guo, Yutao Shen, Hao Wu, Jiayan Luo, Xiaoke Niu, Ruixiang Luo, Yimin Hu, Bo Wang, Lingfeng Chen, Xing Su, Peng Teng, Dawei Jiang, Jianing Zhang, Ruhong Zhou · 发表于：Journal of Medicinal Chemistry · 年份：2026 · DOI：10.1021/acs.jmedchem.6c01140 · 研究领域：Radiopharmaceutical Chemistry and Applications、Peptidase Inhibition and Analysis、Neuroendocrine Tumor Research Advances

Abstract Asialoglycoprotein receptor (ASGPR) is specifically expressed on hepatocytes, making it an attractive target for imaging functional liver reserve. Clinically used ASGPR-targeting radiopharmaceuticals, such as [99mTc]Tc-GSA, are widely employed for this purpose. Here, we report a series of cyclic glycopeptides and evaluate their performance in hepatic imaging in healthy mice. Using a solid-phase peptide synthesis approach, we readily accessed low-molecular-weight cyclic glycopeptides. Cellular uptake studies in hepatocytes identified IPM-G1005 as a lead compound with pronounced uptake. Radiolabeling with gallium-68 afforded [68Ga]Ga-DOTA-IPM-G1005 in high radiochemical yield (>95%) and with excellent stability. In vivo, [68Ga]Ga-DOTA-IPM-G1005 demonstrated rapid and selective hepatic accumulation within 30 min, along with high target-to-background contrast (liver-to-muscle ratio >50). These results highlight that cyclic glycopeptide-based [68Ga]Ga-DOTA-IPM-G1005 represents a promising low-molecular-weight radiopharmaceutical with favorable pharmacokinetics for liver function imaging.