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Bioorg Med Chem ; 35: 116090, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33639594

RESUMEN

Manganese(III) porphyrins (MnIIIPs) as MRI contrast agents (CAs) have drawn particular attention due to their high longitudinal relaxivity (r1) and unique biodistribution. In this work, two MnIIIP-based oligomers, MnPD and MnPT, were designed to further improve the relaxivity with ease of synthesis. The two compounds were fully characterized and their nuclear magnetic relaxation dispersion (NMRD) profiles were acquired with a fast field cycling NMR relaxometer. Both of the compounds exhibited extended high molar r1 at high fields, higher than that of Gd-DTPA, the first clinical gadolinium(III)-based MRI CA. The r1 value of per manganese atom increased with the increasing number of MnIIIP building blocks, suggesting rotational correlation time (τR) played dominant role in the r1 dispersion. The toxicity of the two MnIIIPs and the imaging effectiveness were estimated in vitro and in vivo. With good biocompatibility, significant contrast enhancement, and complete excretion in 24 h, MnPD and MnPT are both promising for high field clinical applications. The applied strategy also potentially provided a facile approach for creation of more MnIIIP oligomer as efficient T1 MRI CAs.


Asunto(s)
Medios de Contraste/química , Imagen por Resonancia Magnética , Metaloporfirinas/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Metaloporfirinas/farmacología , Ratones , Ratones Endogámicos ICR , Estructura Molecular
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