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

## TL;DR

Scientists developed a new PET radiopharmaceutical, [68Ga]Ga-NODAGA-NonaLysan, which shows better liver imaging properties than the current standard [99mTc]Tc-GSA.

## Contribution

A novel 68Ga-labeled glycopeptide with superior liver uptake and imaging properties compared to existing radiotracers.

## Key findings

- 68Ga-labeled glycopeptides with increasing galactose residues showed improved liver uptake in mice.
- [68Ga]Ga-NODAGA-NonaLysan achieved high liver uptake (79.6% ID/g) and better performance than [99mTc]Tc-GSA.
- The radiotracer exhibited good metabolic stability and hydrophilicity, suitable for PET imaging.

## Abstract

[99mTc]Tc-GSA,
an albumin-based glycoprotein, is routinely
used in Japan to measure the asialoglycoprotein receptor (ASGR) density
via single photon emission tomography. Here we describe the development
of 68Ga-labeled peptide-based alternatives. Peptides were
assembled on a solid support using a fragment coupling strategy. Glycosylation
was carried out via a click chemistry approach resulting in a set
of three peptides with increasing amounts of d-galactose
(n = 3, 6, and 9) as well as one glycopeptide bearing
nine N-acetylgalactosamine residues. 68Ga-labeling of all compounds could be achieved in high radiochemical
yields (>95%). Radiotracers exhibited high hydrophilicity, good
metabolic
stability in human serum and protein binding between 12 and 22%. The
IC50 values improved in the series tri-, hexa-, and nonamer
with an IC50 of 50 ± 30 pM for the latter one. In
analogy, the in vivo biodistribution studies revealed
increased liver uptake in the series of [68Ga]Ga-NODAGA-TriLysan (9.4 ± 2.0% ID/g, 30 min p.i.), [68Ga]Ga-NODAGA-HexaLysan (55.5 ± 7.4% ID/g,
30 min p.i.), and [68Ga]Ga-NODAGA-NonaLysan (79.6 ± 8.0% ID/g, 30 min p.i.). [68Ga]Ga-NODAGA-GalNAc-NonaLysan
reached comparable liver uptake to [68Ga]Ga-NODAGA-NonaLysan, but showed higher accumulation in nontarget organs. The impressive
imaging properties of [68Ga]Ga-NODAGA-NonaLysan were also confirmed by the PET/MR imaging studies in mice. Hence,
[68Ga]Ga-NODAGA-NonaLysan represents a new
PET radiopharmaceutical with even better imaging properties than [99mTc]Tc-GSA.