In vivo Overhauser-enhanced MRI of proteolytic activity.
Contrast Media Mol Imaging
; 9(5): 363-71, 2014.
Article
en En
| MEDLINE
| ID: mdl-24729587
ABSTRACT
There is an increasing interest in developing novel imaging strategies for sensing proteolytic activities in intact organisms in vivo. Overhauser-enhanced MRI (OMRI) offers the possibility to reveal the proteolysis of nitroxide-labeled macromolecules thanks to a sharp decrease of the rotational correlation time of the nitroxide moiety upon cleavage. In this paper, this concept is illustrated in vivo at 0.2 T using nitroxide-labeled elastin orally administered in mice. In vitro, this elastin derivative was OMRI-visible and gave rise to high Overhauser enhancements (19-fold at 18 mm nitroxide) upon proteolysis by pancreatic porcine elastase. In vivo three-dimensional OMRI detection of proteolysis was carried out. A keyhole fully balanced steady-state free precession sequence was used, which allowed 3D OMRI acquisition within 20 s at 0.125 mm(3) resolution. About 30 min after mouse gavage, proteolysis was detected in the duodenum, where Overhauser enhancements were 7.2 ± 2.4 (n = 7) and was not observed in the stomach. Conversely, orally administered free nitroxides or pre-digested nitroxide-labeled elastin were detected in the mouse's stomach by OMRI. Combined with specific molecular probes, this Overhauser-enhanced MRI technique can be used to evaluate unregulated proteolytic activities in various models of experimental diseases and for drug testing.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Imagen por Resonancia Magnética
/
Elastina
/
Medios de Contraste
/
Óxidos de Nitrógeno
Límite:
Animals
Idioma:
En
Revista:
Contrast Media Mol Imaging
Asunto de la revista:
DIAGNOSTICO POR IMAGEM
Año:
2014
Tipo del documento:
Article
País de afiliación:
Francia