Effect of resovist on rats with different severities of liver cirrhosis.
OBJECTIVE
Whether the degree of diffuse hepatic damage is correlated with the signal change on MR images after injection of superparamagnetic iron oxide (SPIO) particles was investigated. In addition, we investigated whether hepatic function deteriorates after injection of SPIO.


METHODS
Seventy-six female Sprague-Dawley rats aged 3 to 4 weeks were given drinking water containing 0.03% thioacetamide (TAA) for 4 or 12 weeks to induce two grades of liver injury. Seventeen normal rats were served as a control. Normal and model rats were administered Resovist (10 micromol Fe/kg), and signal intensities in the liver on MR images obtained at 4.7 T were measured up to 60 minutes after injection (n = 5). The model rats were injected with 10 times the envisaged dose of Resovist (100 micromol Fe/kg) or saline as a control substance, and blood parameters were measured at 4, 24, and 48 hours after injection (n = 5 or 6). At 4 hours after injection, iron and Kupffer cells in the liver were stained (n = 3).


RESULTS
Maximal signal reduction in the liver occurred 15 minutes after injection in all groups. The reduced signal persisted for 60 minutes after injection. However, the degree of maximal signal reduction in the model rats was significantly less than that in the normal rats (P < 0.05, 0.01). Signal reduction in the 12-week group was less than that in the 4-week group. In control rats, the number of iron-positive cells increased by 22 cells per area (0.065 mm(2)) following treatment with Resovist. In the 4-week and 12-week groups, numbers of iron-positive cells increased by 13 and 11 cells, respectively. There was no statistically significant difference in the number of Kupffer cells between control and model rats. No significant change was observed in blood parameters with Resovist.


CONCLUSIONS
The MR signal induced by Resovist depended on the degree of phagocytic activity in the liver. The safety profiles of Resovist remained unchanged even at 10 times the imaging dose.
Kato
Naoki
N
Drug Discovery Institute, Nihon Schering K.K., Yodogawa-ku, Osaka, Japan. nkatoh@schering.co.jp
Ihara
Shinya
S
Tsujimoto
Taichi
T
Miyazawa
Tomoaki
T
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage*; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide; D007501:Iron / Q000008:administration & dosage* / Q000032:analysis; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology*; D008111:Liver Function Tests; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D010087:Oxides / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide