Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide The exclusive asialoglycoprotein receptor (ASGR) expression on hepatocytes makes it an attractive target for imaging of the functional liver reserve. Here, we present a set of TRAP-based glycoside trimers and evaluate their imaging properties compared to the gold standard [ 99m Tc]Tc-GSA. The click-chemistry-based synthesis approach provided easy access to trimeric low-molecular-weight compounds. Labeling with 68 Ga was carried out in high radiochemical yields (>99%). Complexes showed high stability and hydrophilicity. Protein binding ranged between 10 and 25%. Highest binding affinity (IC 50 ) and best liver accumulation were found for [ 68 Ga]Ga- T3N3, followed by [ 68 Ga]Ga- T3G3 and [ 68 Ga]Ga- T0G3 . Rapid elimination from the rest of the body resulted in excellent target-to-background ratios. Our studies confirmed that high ASGR uptake depends on the correct spacer design and that N -acetylgalactosamine improves targeting properties in vivo . Thus, [ 68 Ga]Ga- T3N3 represents a new low-molecular-weight radiopharmaceutical with pharmacokinetics similar to those of [ 99m Tc]Tc-GSA.
Source: Journal of Medicinal Chemistry
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funder: Austrian Science Fund
OpenAlex ID: W4403465598