⁶⁸Ga-Labeled Glycopeptides as Effective Tools for Liver Function Imaging.

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Molecular Imaging

Background:

• Technetium-99m labeled-Galanin-Gallium-68 (^99mTc]Tc-GSA is a standard for measuring asialoglycoprotein receptor (ASGR) density using single photon emission tomography.
• Development of novel positron emission tomography (PET) radiotracers is crucial for improved diagnostic capabilities.

Purpose of the Study:

• To develop and evaluate Gallium-68 (⁶⁸Ga)-labeled peptide-based radiotracers as potential alternatives to [^99mTc]Tc-GSA for ASGR imaging.
• To assess the binding affinity, stability, and *in vivo* performance of novel glycopeptides.

Main Methods:

• Peptide synthesis using solid-phase fragment coupling and click chemistry for glycosylation.
• ⁶⁸Ga-labeling of synthesized glycopeptides.
• Evaluation of radiotracers' hydrophilicity, metabolic stability, protein binding, and IC₅₀ values.
• *In vivo* biodistribution studies and PET/MR imaging in mice.

Main Results:

• High radiochemical yields (>95%) achieved for all ⁶⁸Ga-labeled glycopeptides.
• The nonamer peptide ([⁶⁸Ga]Ga-NODAGA-NonaLysan) showed the highest binding affinity (IC₅₀ = 50 ± 30 pM).
• *In vivo* studies demonstrated significantly increased liver uptake for [⁶⁸Ga]Ga-NODAGA-HexaLysan and [⁶⁸Ga]Ga-NODAGA-NonaLysan compared to shorter peptides.
• [⁶⁸Ga]Ga-NODAGA-NonaLysan exhibited excellent imaging properties in PET/MR studies, surpassing [^99mTc]Tc-GSA.

Conclusions:

• ⁶⁸Ga-labeled peptide-based tracers, particularly [⁶⁸Ga]Ga-NODAGA-NonaLysan, are promising PET radiopharmaceuticals for ASGR imaging.
• These novel tracers offer improved imaging characteristics compared to the current standard [^99mTc]Tc-GSA.
• The developed methodology allows for the creation of targeted radiotracers for liver receptor imaging.