Macrocyclic paramagnetic agents for MRI: Determinants of relaxivity and strategies for their improvement.
Magn Reson Med
; 78(4): 1523-1532, 2017 10.
Article
en En
| MEDLINE
| ID: mdl-27791281
ABSTRACT
PURPOSE:
To dissect the contributions to the longitudinal relaxivity (r1 ) 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 r1 .METHODS:
Longitudinal relaxation rates R1 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 r1 values.RESULTS:
In v-SBF or in the presence of HSA, r1 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-1 s-1 for Gd-DOTA, Gd-HPDO3A, and Gd-Phen-DO3A, respectively. R1 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 r1 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 r1 as a result of an improved interaction with plasma's macromolecules and the shift of the prototropic exchange to physiological pH. Magn Reson Med 781523-1532, 2017. © 2016 International Society for Magnetic Resonance in Medicine.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Organometálicos
/
Imagen por Resonancia Magnética
/
Medios de Contraste
/
Compuestos Heterocíclicos
Límite:
Humans
Idioma:
En
Revista:
Magn Reson Med
Asunto de la revista:
DIAGNOSTICO POR IMAGEM
Año:
2017
Tipo del documento:
Article
País de afiliación:
Italia