Calix[4]arenes as Molecular Platforms for Magnetic Resonance Imaging (MRI) Contrast Agents

The novel amphipilic conjugate of a calix[4]arene with four Gd–1,4,7,10‐ tetra(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane (DOTA) chelates has potential as a magnetic resonance imaging contrast agent, both in its monomeric and in its micellar form. The system, illustrated here with its nuclear mag...

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Bibliographic Details
Published in:Chemistry : a European journal Vol. 15; no. 13; pp. 3290 - 3296
Main Authors: Schühle, Daniel T., Schatz, Jürgen, Laurent, Sophie, Vander Elst, Luce, Muller, Robert N., Stuart, Marc C. A., Peters, Joop A.
Format: Journal Article
Language:English
Published: Weinheim WILEY-VCH Verlag 16.03.2009
WILEY‐VCH Verlag
Wiley
Subjects:
Algorithms
calixarenes
Calixarenes - chemistry
Chemistry
Chemistry, Multidisciplinary
gadolinium
Gadolinium - chemistry
human serum albumin
Humans
Magnetic Resonance Imaging - methods
Micelles
Models, Chemical
molecular imaging
Organometallic Compounds - chemistry
Organophosphorus Compounds - chemistry
Phenols - chemistry
Physical Sciences
Science & Technology
Serum Albumin - chemistry
calixarenes
HUMAN SERUM-ALBUMIN
GD-III COMPLEX
SENSITIVITY
WATER EXCHANGE
micelles
molecular imaging
GADOLINIUM(III)
HIGH-RELAXIVITY
NMR
BINDING-AFFINITY
ENHANCEMENT
OPTIMIZATION
human serum albumin
gadolinium
ISSN:0947-6539, 1521-3765
Online Access:Get full text
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Summary:The novel amphipilic conjugate of a calix[4]arene with four Gd–1,4,7,10‐ tetra(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane (DOTA) chelates has potential as a magnetic resonance imaging contrast agent, both in its monomeric and in its micellar form. The system, illustrated here with its nuclear magnetic relaxation profile, shows good relaxivities, thanks to its high rigidity. An amphiphilic conjugate 1 of a calix[4]arene with four Gd–DOTA chelates (DOTA=1,4,7,10‐tetra(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane) was prepared and the properties relevant to its application as a magnetic resonance imaging (MRI) contrast agent were investigated by NMR, dynamic light scattering (DLS), and cryo‐electron microscopy (cryo‐TEM). The compound aggregates in water; its critical micelle concentration (cmc) is 0.21 mM (or 0.84 mM for Gd) at 37 °C. The relaxivity of the aggregates at 37 °C and 20 MHz (18.3 s−1 per mM Gd or 73.2 s−1 per mM 1) is about twice that of the monomer. Nuclear magnetic relaxation dispersion (NMRD) profiles show the relaxivity of the monomer to be almost independent of the magnetic field strength up to 60 MHz. At higher concentrations, the NMRD profiles exhibit a maximum at about 20 MHz, which is typical for high molecular volumes. The average water residence lifetime is 1.20 μs at 298 K as determined by 17O NMR. The rotational correlation time of the monomer (390 ns at 37 °C) is very close to the optimal value predicted for high‐field contrast agents. Monomer as well as micelles are very rigid systems with negligible local contributions to the overall rotational dynamics. The binding to human serum albumin (HSA) is significant (KA=1.2×103 M−1) and the relaxivity of the HSA adduct at 20 MHz is 24.6 s−1 per mM Gd or 98.5 s−1 per mM 1. The novel amphipilic conjugate of a calix[4]arene with four Gd–1,4,7,10‐ tetra(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane (DOTA) chelates has potential as a magnetic resonance imaging contrast agent, both in its monomeric and in its micellar form. The system, illustrated here with its nuclear magnetic relaxation profile, shows good relaxivities, thanks to its high rigidity.
Bibliography:ArticleID:CHEM200802099
istex:0FF3E110202DAE92F389178787FC225982070F97
Marie-Curie Fellowship - No. MEST-CT-2004-7442
COST D38
European Network of Excellence - No. LSCH-2004-503569
ark:/67375/WNG-1P17ZXXW-1
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.200802099