Gallium-68 Labeled Cyclic Glycopeptides for Liver Function Imaging

Area of Science:

• Biomedical imaging
• Radiopharmaceutical chemistry
• Hepatology

Background:

• The asialoglycoprotein receptor (ASGPR) is highly expressed on hepatocytes, making it a key target for liver function imaging.
• Current ASGPR-targeting agents like [99mTc]Tc-GSA are used clinically, but novel agents are needed.

Purpose of the Study:

• To develop and evaluate novel low-molecular-weight cyclic glycopeptides for ASGPR-targeted hepatic imaging.
• To identify a lead compound with high hepatocyte uptake and favorable characteristics for radiolabeling and in vivo imaging.

Main Methods:

• Synthesis of cyclic glycopeptides using solid-phase peptide synthesis.
• In vitro cellular uptake studies in hepatocytes to identify lead compounds.
• Radiolabeling with Gallium-68 (68Ga) and stability assessment.
• In vivo biodistribution studies in healthy mice to evaluate hepatic accumulation and target-to-background ratios.

Main Results:

• IPM-G1005 was identified as a lead compound with significant hepatocyte uptake.
• [68Ga]Ga-DOTA-IPM-G1005 was prepared with high radiochemical yield (>95%) and excellent stability.
• In vivo studies showed rapid and selective liver accumulation of [68Ga]Ga-DOTA-IPM-G1005 within 30 minutes, achieving a liver-to-muscle ratio >50.

Conclusions:

• Cyclic glycopeptide-based [68Ga]Ga-DOTA-IPM-G1005 is a promising low-molecular-weight radiopharmaceutical.
• The agent exhibits favorable pharmacokinetics for effective liver function imaging.
• This novel tracer holds potential for clinical applications in assessing hepatic reserve.