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

Patty Wong, Lin Li, Junie Chea, Weidong Hu, Erasmus Poku, Todd Ebner, Nicole Bowles, Jeffrey Y.C. Wong, Paul J. Yazaki, Stephen Sligar, John E. Shively

Research output: Contribution to journalArticle

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 64Cu. 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 64Cu-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.

Original languageEnglish (US)
Pages (from-to)743-753
Number of pages11
JournalBioconjugate Chemistry
Volume31
Issue number3
DOIs
StatePublished - Mar 18 2020

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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    Wong, P., Li, L., Chea, J., Hu, W., Poku, E., Ebner, T., Bowles, N., Wong, J. Y. C., Yazaki, P. J., Sligar, S., & Shively, J. E. (2020). Antibody Targeted PET Imaging of 64Cu-DOTA-Anti-CEA PEGylated Lipid Nanodiscs in CEA Positive Tumors. Bioconjugate Chemistry, 31(3), 743-753. https://doi.org/10.1021/acs.bioconjchem.9b00854