Work

Antibody Targeted PET Imaging of 64 Cu-DOTA-Anti-CEA PEGylated Lipid Nanodiscs in CEA Positive Tumors

Year: 2020

Type: article

Abstract: Lipid nanodiscs (LNDs), comprising a phospholipid bilayer encircled by two molecules of a recombinant membrane scaffold protein, can be targeted to tumors with covalently attached antibodies (Abs) or their fragments. Antibody attachment to click chemistry based PEGylated lipids on LNDs including DOTA allowed PET imaging with the positron emitter 64 Cu. Carcinoembryonic antigen (CEA) positive tumors in CEA transgenic mice were chosen as a tumor target. Fab′ fragments, that otherwise are rapidly cleared by the kidney due to their small size, were retained in circulation when conjugated to LNDs. Untargeted PET imaging of 64 Cu-DOTA-LNDs revealed low tumor uptake (4–5% ID/g) in the range expected for the enhanced permeability retention (EPR) effect with high liver uptake (17–21% ID/g) indicating gut clearance. Fab′ targeted LNDs showed little improvement over untargeted LNDs, but intact IgG targeted LNDs gave high tumor uptake (40% ID/g) with low liver (8% ID/g), demonstrating that tumor targeting with antibody conjugated LNDs is feasible.

Source: Bioconjugate Chemistry

DOI: 10.1021/acs.bioconjchem.9b00854