Molecular imaging by micro-CT: specific E-selectin imaging.
The primary goal of this study was to design a fluorescent E-selectin-targeted iodine-containing liposome for specific E-selectin imaging with the use of micro-CT. The secondary goal was to correlate the results of micro-CT imaging with other imaging techniques with cellular resolution, i.e., confocal and intravital microscopy. E-selectin-targeted liposomes were tested on endothelial cells in culture and in vivo in HT-29 tumor-bearing mice (n = 12). The liposomes contained iodine (as micro-CT contrast medium) and fluorophore (as optical contrast medium) for confocal and intravital microscopy. Optical imaging methods were used to confirm at the cellular level, the observations made with micro-CT. An ischemia-reperfusion model was used to trigger neovessel formation for intravital imaging. The E-selectin-targeted liposomes were avidly taken up by activated endothelial cells, whereas nontargeted liposomes were not. Direct binding of the E-selectin-targeted liposomes was proved by intravital microscopy, where bright spots clearly appeared on the activated vessels. Micro-CT imaging also demonstrated accumulation of the targeted lipsomes into subcutaneous tumor by an increase of 32 + or - 8 HU. Hence, internalization by activated endothelial cells was rapid and mediated by E-selectin. We conclude that micro-CT associated with specific molecular contrast agent is able to detect specific molecular markers on activated vessel walls in vivo.
University Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Caroline
C
Wyss
Stephan C
SC
Schaefer
Lucienne
L
Juillerat-Jeanneret
Lucienne
L
Lagopoulos
Hans-Anton
HA
Lehr
Christoph D
CD
Becker
Xavier
X
Montet
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D003287:Contrast Media; D019040:E-Selectin / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014057:Tomography, X-Ray Computed / Q000379:methods*
D014408:Biomarkers, Tumor; D003287:Contrast Media; D019040:E-Selectin