A beta-cyclodextrin "click cluster" decorated with seven paramagnetic chelates containing two water exchange sites.
The development of novel macromolecular contrast agents that offer enhanced relaxivity profiles at high magnetic fields have the potential to greatly improve the diagnosis, understanding, and treatment of disease. To this end, we have designed a monodiperse paramagnetic beta-cyclodextrin click cluster decorated with seven paramagnetic arms. A novel alkyne-functionalized diethylenetriaminetetraacetic acid (DTTA) chelate (6) has been created and coupled to a per-azido-beta-cyclodextrin core (7) to yield the precursor macromolecule (8). After removal of the protecting groups and titrating with Gd (3+), the final paramagnetic click cluster, Gd10, was obtained. Luminescence measurements were carried out in H 2O and D 2O on an analogous structure, Eu10, and indicated that at each lanthanide has an average of 1.8 water exchange sites, which is important for enhancing relaxivity and MRI resolution. This discrete paramagnetic click cluster yields a high relaxivity profile (43.4 mM (-1) s (-1) per molecule and 6.2 mM (-1) s (-1) per Gd (3+) at 9.4 T) and enhanced contrast on a human MRI scanner as compared to a commercial agent, Magnevist (3.2 mM (-1) s (-1) at 9.4 T). Moreover, the useful inclusion properties exhibited by beta-cyclodextrin also make this an excellent host scaffold to functionalize via noncovalent assembly with receptor specific targeting moieties for biomolecular imaging.
Bryson
Joshua M
JM
The Department of Chemistry at Virginia Tech, Blacksburg, Virginia 24061, USA.
Chu
Wen-Jang
WJ
Lee
Jing-Huei
JH
Reineke
Theresa M
TM
D002614:Chelating Agents / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D014867:Water / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D002614:Chelating Agents; D003287:Contrast Media; D047392:beta-Cyclodextrins; D014867:Water; C031215:betadex