Cell labeling via membrane-anchored lipophilic MR contrast agents.
Cell tracking in vivo with MR imaging requires the development of contrast agents with increased sensitivity that effectively label and are retained by cells. Most clinically approved Gd(III)-based contrast agents require high incubation concentrations and prolonged incubation times for cellular internalization. Strategies to increase contrast agent permeability have included conjugating Gd(III) complexes to cell penetrating peptides, nanoparticles, and small molecules which have greatly improved cell labeling but have not resulted in improved cellular retention. To overcome these challenges, we have synthesized a series of lipophilic Gd(III)-based MR contrast agents that label cell membranes in vitro. Two of the agents were synthesized with a multiplexing strategy to contain three Gd(III) chelates (1 and 2) while the third contains a single Gd(III) chelate (3). These new agents exhibit significantly enhanced labeling and retention in HeLa and MDA-MB-231-mcherry cells compared to agents that are internalized by cells (4 and Prohance).
Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
Christiane E
CE
Carney
Keith W
KW
MacRenaris
Daniel J
DJ
Mastarone
David R
DR
Kasjanski
Andy H
AH
Hung
Thomas J
TJ
Meade
D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry*; D049109:Cell Proliferation; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008279:Magnetic Resonance Imaging; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties
D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium