Bifunctional Chelates Optimized for Molecular MRI
| Autor: | Marie-Caline Abadjian, Erik C. Wiener, Arnold L. Rheingold, Po Yee Leung, Raghvendra S. Sengar, Douglas B. Grotjahn, Curtis E. Moore, Christie Schulte, Christoffel van Niekerk, Luce Vander Elst |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Relaxometry Stereochemistry Gadolinium Biotin Contrast Media chemistry.chemical_element Article Inorganic Chemistry chemistry.chemical_compound Models DOTA Chelation Physical and Theoretical Chemistry Bifunctional Chelating Agents biology Molecular Magnetic Resonance Imaging Combinatorial chemistry Quaternary Ammonium Compounds Enantiopure drug chemistry Covalent bond biology.protein Inorganic & Nuclear Chemistry Other Chemical Sciences Physical Chemistry (incl. Structural) Avidin |
| Zdroj: | Inorganic Chemistry Inorganic chemistry, vol 53, iss 13 |
| ISSN: | 1520-510X 0020-1669 |
| DOI: | 10.1021/ic500085g |
| Popis: | Important requirements for exogenous dyes or contrast agents in magnetic resonance imaging (MRI) include an effective concentration of paramagnetic or superparamagnetic ions at the target to be imaged. We report the concise synthesis and characterization of several new enantiopure bifunctional derivatives of (α1R,α4R,α7R,α10R)-α1,α4,α7,α10-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTMA) (and their 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) analogues as controls) that can be covalently attached to a contrast agent delivery system using either click or peptide coupling chemistry. Gd complexes of these derivatives can be attached to delivery systems while maintaining optimal water residence time for increased molecular imaging sensitivity. Long chain biotin (LC-biotin) derivatives of the Eu(III) and Gd(III) chelates associated with avidin are used to demonstrate higher efficiencies. Variable-temperature relaxometry, 17O NMR, and nuclear magnetic resonance dispersion (NMRD) spectroscopy used on the complexes and biotin–avidin adducts measure the influence of water residence time and rotational correlation time on constrained and unconstrained systems. The Gd(III)-DOTMA derivative has a shorter water residence time than the Gd(III)-DOTA derivative. Compared to the constrained Gd(III)-DOTA derivatives, the rotationally constrained Gd(III)-DOTMA derivative has ∼40% higher relaxivity at 37 °C, which could increase its sensitivity as an MRI agent as well as reduce the dose of the targeting agent. Multigram preparation of enantiopure bifunctional derivatives of DOTMA for Gd-based contrast agents will enable coupling to targeting systems via click or amide-bond chemistry. The Gd(III)-DOTMA derivative has a shorter water residence time than the Gd(III)-DOTA derivative. Using biotin−avidin complexation to compare constrained systems, the Gd(III)-DOTMA derivative has ∼40% higher relaxivity at 37 °C compared to the DOTA analogue, which could increase its sensitivity as an efficient MRI agent. |
| Databáze: | OpenAIRE |
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