Schematic comparison of glycan-targeting versus traditional (glyco)protein targeting for molecular imaging of tumors. (a) Tumor-associated glycans (dark blue branches) are densely packed on multiple proteins (displayed in pink and dark blue) with higher density than binding epitopes on tumor-associated proteins (displayed in yellow). This may result in a denser accumulation of conjugated antibodies, subsequently enhancing tumor signal during imaging. (b) Glycans form the outer layer of proteins, making them easily accessible to administered targeting moieties. Noteworthily, glycans may mask binding domains on proteins, challenging specific binding of protein-directed targeting moieties. (c) Since aberrantly expressed glycans may be expressed on many glycoproteins (amplified expression), changes in glycoprotein glycosylation are more attractive for use as serum biomarkers than targeting of individual glycoproteins. (d) As similar tumor-associated glycan structures are expressed on multiple tumor-associated proteins, glycan-targeting can be more efficient compared to single protein targeting.