Mechanism of hepatic parenchyma-specific contrast of microbubble-based contrast agent for ultrasonography: microscopic studies in rat liver.
OBJECTIVE
The objective of this study was to elucidate the mechanism of hepatic parenchyma-specific contrast of Sonazoid (microbubble contrast agent) using microscopic techniques.


METHODS
Sonazoid was intravenously injected into rats to investigate the microbubble dynamics and distribution within hepatic microcirculation in exteriorized liver using intravital microscopy and to observe dose dependency of ultrasound hepatic contrast effect. In vitro and in vivo uptake of microbubbles by Kupffer cells was examined using confocal laser scanning microscopy.


RESULTS
Intravital observation demonstrated freely flowing microbubbles in the sinusoid and some microbubbles co-localized with Kupffer cells. The microbubbles internalized in Kupffer cells were identified with reflected light by confocal laser scanning microscopy. The percentage of Kupffer cells taking up microbubbles was about 1% at clinical dose at which the homogeneous hepatic contrast was observed.


CONCLUSIONS
The hepatic parenchyma-specific contrast by Sonazoid is due to distribution of the microbubbles in Kupffer cells.
Watanabe
Rira
R
R&D Division, Daiichi Pharmaceutical Co., Ltd, Tokyo, Japan. watanabe.rira.vi@daiichisankyo.co.jp
Matsumura
Manabu
M
Munemasa
Toshiko
T
Fujimaki
Masayoshi
M
Suematsu
Makoto
M
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D005290:Ferric Compounds / Q000493:pharmacokinetics*; D007501:Iron / Q000493:pharmacokinetics*; D007728:Kupffer Cells / Q000166:cytology / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D045423:Microbubbles; D009928:Organ Specificity; D010087:Oxides / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014463:Ultrasonography / Q000379:methods
D003287:Contrast Media; D005290:Ferric Compounds; D010087:Oxides; C069727:Sonazoid; D007501:Iron