[Synthesis of Gal-BSA-SPIO and magnetic resonance imaging of ASG receptors in rabbits bearing liver VX2 tumor and human liver].
OBJECTIVE
To synthesize Gal-BSA-SPIO as the magnetic resonance imaging (MRI) contrast agent targeting asialoglycoprotein (ASG) receptors in the liver and observe its role in MRI detection of hepatocellular carcinomas (HCCs).


METHODS
Gal-BSA was synthesized by means of reductive amination and mixed with SPIO in ice bath to prepare Gal-BSA-SPIO complex. Twenty rabbits bearing VX2 liver tumor underwent MRI enhanced by SPIO (n=10) and Gal-BSA-SPIO (n=10), and the T2 values of the liver and tumor before and after the contrast imaging were measured. Fresh human normal hepatic tissues (n=3), cirrhotic tissues (n=4) and HCC tissues (n=6) were obtained and incubated with Gal-BSA-SPIO followed by Perl's Prussian blue staining to observe the distribution of ASG receptors.


RESULTS
The size of the Gal-BSA-SPIO particles was 34.4 nm. The 20 rabbits bearing VX2 tumor, with tumor size ranging from 3 mm to 12 mm, showed isointense signal in the liver and hypointense signal in the tumor on T1WI, and isointense signal in the liver and slightly hyperintense signal in the tumor on GRE T2*WI. The signal intensity of the liver decreased slightly or moderately after administration of SPIO in the rabbits, and administration Gal-BSA-SPIO resulted in obvious reduction in the signal intensity of the liver. The signal intensities of the tumors did not exhibit obvious changes after the administration of SPIO or Gal-BSA-SPIO. Histological examination revealed numerous blue iron deposits in the Kupffer cells in SPIO group and in the hepatocytes in Gal-BSA-SPIO group, but not in the tumors in either of the groups. The human liver specimens incubated with Gal-BSA-SPIO contained numerous blue iron deposits in the hepatocyte cytoplasm and cell membrane in normal liver tissue, but the deposits were reduced in the cirrhotic tissue and almost absent in the HCC tissue.


CONCLUSIONS
Gal-BSA-SPIO can specifically bind to ASG receptors on hepatocyte membrane to improve the tumor-liver contrast-to-noise ratio.
Jia
Fei-ge
FG
Diagnostic Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. jiafeige@yahoo.com.cn
Zhang
Xiao-dong
XD
Xu
Yi-kai
YK
Meng
Zhuo
Z
D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000737:chemistry / Q000378:metabolism*; D003287:Contrast Media / Q000138:chemical synthesis*; D003911:Dextrans; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D052203:Ferrosoferric Oxide / Q000737:chemistry; D005690:Galactose / Q000737:chemistry; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000737:chemistry
D037263:Asialoglycoprotein Receptor; D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D012710:Serum Albumin, Bovine; C065507:ferumoxides; D005690:Galactose; D052203:Ferrosoferric Oxide