Gallium-68LabeledCyclic Glycopeptides for LiverFunction Imaging

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.