Purpose: To dissect the contributions to the longitudinal relaxivity (r ) of two commercial contrast agents (CAs), Gd-DOTA and Gd-HP-DO3A, and to synthesize/characterize a novel macrocyclic agent (Gd-Phen-DO3A) having superior r .
Methods: Longitudinal relaxation rates R of the CAs in saline with/without human serum albumin (HSA), ionized simulated body fluid (i-SBF), viscous simulated body fluid (v-SBF), and human plasma were measured. Results have been interpreted to evince the main determinants to the observed r values.
Results: In v-SBF or in the presence of HSA, r is enhanced for all complexes, reflecting the viscosity increase and a weak interaction with proteins. The CAs further differentiate in plasma, with a relaxivity increase (versus saline) of approximately 1, 1.5, and 2.5 mM s for Gd-DOTA, Gd-HPDO3A, and Gd-Phen-DO3A, respectively. R versus pH curves in i-SBF indicates that prototropic exchange sizably contributes to the relaxivity of Gd-HP-DO3A and Gd-Phen-DO3A.
Conclusion: The major contributions to r in the physiological environment have been highlighted, namely, increased viscosity, complex-protein interaction, and prototropic exchange. The control of these terms allows the design of novel macrocyclic structures with enhanced r as a result of an improved interaction with plasma's macromolecules and the shift of the prototropic exchange to physiological pH. Magn Reson Med 78:1523-1532, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/mrm.26519 | DOI Listing |
Molecules
September 2024
Department of Science and Technological Innovation, Università del Piemonte Orientale, Viale T. Michel 11, 15121 Alessandria, Italy.
In the last three decades, high-relaxivity Magnetic Resonance Imaging (MRI) contrast agents (CAs) have been intensively sought, aiming at a reduction in the clinically injected dose while maintaining the safety of the CA and obtaining the same pathological information. Thus, four new Gd(III) complexes based on modified 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) macrocyclic structure were designed and synthesized by introducing further polar and protic functional groups (amides, phosphonates, and diols) adjacent to the metal-coordinated hydroxyl group. A detailed H NMR relaxometric analysis allowed us to investigate the effect of these functional groups on the relaxivity, which showed a 20-60% increase (at 0.
View Article and Find Full Text PDFJ Phys Chem A
May 2024
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, Favorsky st. 1, Irkutsk 664033, Russia.
The conformational analysis of nine functionalized 1,2,3-triazoles was carried out by the correlation of calculated and experimental high-level nuclear magnetic resonance (NMR) chemical shifts. In solution, the studied triazoles are in exchange dynamic equilibrium caused by their prototropic tautomerism of the NH-proton. The experimentally unresolved NMR signals were assigned for most of the compounds.
View Article and Find Full Text PDFInorg Chem
March 2024
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
This study was designed to test whether the single appended phosphonate group in GdDOTA-1AmP is sufficient for catalyzing the exchange of proton from the single inner-sphere water-exchanging molecule. Unlike the other phosphonate derivatives in this series, GdDOTA-1AmP showed a surprisingly smooth increase in relaxivity from 3.0 to 6.
View Article and Find Full Text PDFJ Am Chem Soc
January 2024
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy.
Gd-L1 is a macrocyclic Gd-HPDO3A derivative functionalized with a short spacer to a trisulfonated pyrene. When compared to Gd-HPDO3A, the increased relaxivity appears to be determined by both the higher molecular weight and the occurrence of an intramolecularly catalyzed prototropic exchange of the coordinated OH moiety. In water, Gd-L1 displayed a relaxivity of 7.
View Article and Find Full Text PDFChemphyschem
June 2022
Department of Chemistry, Birla Institute of Technology and Sciences-Pilani Hyderabad Campus, Shameerpet, Hyderabad, 500078, Telangana, India.
A series of oxidized di(indolyl)arylmethanes (DIAM) with polyaromatic signaling moieties have been designed for monitoring local pH at the interfacial region of surfactant aggregates, such as micelles and vesicles. The oxidized DIAMs show changes in solution color from red to yellow when incorporated in cationic surfactants (at pH 7.4) and yellow to reddish pink when exposed to negatively-charged surfactants (at pH 5.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!