Toxicity and safety evaluation of multivalent lactoside for asialoglycoprotein receptor imaging

Objectives The asialoglycoprotein receptor (ASGP-R) is present only in mammalian liver and is located on the surface hepatocyte membrane. It is specific for asialoglycoproteins (ASGPs), that is desialylated glycoproteins with terminal galactose (Gal) or N-acetylgalactosamine (GalNAc) residues. Previously we developed a novel multivalent lactoside ligand with high affinity and specificity to the ASGP-R. The ligand has been radiolabeled with In-111. Biodistribution and microSPECT/CT imaging in mice showed that this ligand rapid and specifically localized to liver at 15 min after i.v. injection. In this study, we tested the toxicity of this multivalent lactoside to hepatocytes at cellular level for safety evaluation this potential liver function imaging agent.

Methods Cellular toxicity studies including LDH cytotoxicity and WST-1 cell proliferation assay were tested with rodent primary hepatocytes and liver cell lines. The assays were performed with ligand concentration ranged from 0 nM to 1000 nM up to 48 h.

Results LDH cytotoxicity assay demonstrated that the multivalent lactoside had no effect on LDH release of both rodent primary hepatocytes and liver cell lines. WST-1 cell proliferation assay also showed the similar results.

Conclusions Cellular toxicity studies showed that the multivalent lactoside had no effect on LDH release and proliferation of rodent hepatocytes at high drug concentration. The results of this study warranted the potential of this hepatocyte-targeted ligand for liver function imaging and liver-specific drug delivery