<sup>68</sup>Ga-Labeled TRAP-Based Glycoside Trimers\nfor Imaging of the Functional Liver Reserve

The exclusive asialoglycoprotein receptor (ASGR) expression\non\nhepatocytes makes it an attractive target for imaging of the functional\nliver reserve. Here, we present a set of TRAP-based glycoside trimers\nand evaluate their imaging properties compared to the gold standard\n[<sup>99m</sup>Tc]Tc-GSA. The click-chemistry-based synthesis approach\nprovided easy access to trimeric low-molecular-weight compounds. Labeling\nwith <sup>68</sup>Ga was carried out in high radiochemical yields\n(>99%). Complexes showed high stability and hydrophilicity. Protein\nbinding ranged between 10 and 25%. Highest binding affinity (IC<sub>50</sub>) and best liver accumulation were found for [<sup>68</sup>Ga]Ga-<b>T3N3</b>, followed by [<sup>68</sup>Ga]Ga-<b>T3G3</b> and [<sup>68</sup>Ga]Ga-<b>T0G3</b>. Rapid elimination from\nthe rest of the body resulted in excellent target-to-background ratios.\nOur studies confirmed that high ASGR uptake depends on the correct\nspacer design and that <i>N</i>-acetylgalactosamine improves\ntargeting properties <i>in vivo</i>. Thus, [<sup>68</sup>Ga]Ga-<b>T3N3</b> represents a new low-molecular-weight radiopharmaceutical\nwith pharmacokinetics similar to those of [<sup>99m</sup>Tc]Tc-GSA.