Molecular imaging contrast media for visualization of liver function.
OBJECTIVE
Diagnosis of liver disease has improved because of progress in imaging technology. Among the imaging methods, magnetic resonance imaging (MRI) has the advantage of a lack of radiation exposure, but the basis of the method (imaging of hydrogen atoms in water molecules) makes it hard to detect changes in tissue or the location of the diseased tissue in the liver. The aims of this study are to develop new contrast media for visualization of functional changes in the liver and to check the effectiveness of the media.


METHODS
We developed a new molecular imaging contrast media that targets the asialoglycoprotein receptor (ASGP-R), a membrane protein that is specific to hepatocytes. We first checked the contrast media diameter and the cytotoxicity. Next, we examined the interaction of the media with ASGP-R through observation of fluorescein isothiocyanate (FITC)-labeled molecular imaging contrast media bound to normal hepatocellular ASGP-R using confocal laser scanning microscopy. Finally, we used MRI to observe hepatocyte interactions with the molecular imaging contrast media.


RESULTS
The contrast media forms a nanoparticle of about 30 nm diameter in aqueous solution and the cytotoxicity is low. In vitro, the media has high specificity for ASGP-R in normal rat hepatocyte RLN-8 cells and this interaction was blocked by lactose (which has a similar molecular structure to that of galactose) and by an anti-ASGP-R antibody. The contrast media markedly enhanced T1-weighted images in MRI of normal rat hepatocytes compared to the signal strength for rat liver cancer cells.


CONCLUSIONS
We have shown that our new contrast media for molecular imaging of hepatocytes by MRI is effective in vitro.
Yoshinori
Matsuoka
M
Department of Disaster and Emergency Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Kyushu, Japan. yoshinori216@h2.dion.ne.jp
Masaharu
Murata
M
Yuri
Huzisaki
H
Sayoko
Narahara
N
Nao
Shinzato
S
Makoto
Hashizume
H
D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D002460:Cell Line; D003287:Contrast Media; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D007089:Image Enhancement / Q000379:methods*; D008111:Liver Function Tests / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015336:Molecular Probe Techniques; D051381:Rats
D037263:Asialoglycoprotein Receptor; D003287:Contrast Media