Hepatocyte-targeted nuclear imaging using 99mTc-galactosylated chitosan: conjugation, targeting, and biodistribution.
Galactosyl-methylated chitosan (GMC) is a galactosylated chitosan (GC) that is chemically modified to improve labeling efficiency with (99m)Tc compared with native GC. The aim of this study was to investigate the possibility of liver-targeted nuclear imaging with (99m)Tc-GMC bound to asialoglycoprotein receptors (ASGP-R).


METHODS
GMC was obtained after the coupling of lactobionic acid, as the galactose moiety, and methyl iodide with chitosan. Using GMC-labeled fluorescein isothiocyanate (FITC-GMC), we examined whether GMC was localized in hepatocytes. After injection via the tail vein of mice with (99m)Tc-GMC and galactose-free (99m)Tc-methylated chitosan (MC), images were acquired with a gamma-camera equipped with a pinhole collimator. Biodistribution was obtained from 10, 60, and 120 min after injection.


RESULTS
The composition of galactose groups in GC and tri-, di-, and monomethylated GC was confirmed by nuclear magnetic resonance spectroscopy. FITC-GMC was primarily positioned in hepatocytes, and not in Kupffer cells, of the mouse with a scattered pattern. The gamma-camera images showed rapid localization of (99m)Tc-GMC to liver. The percentage injected doses per gram (%ID/g) of liver were 11.155 +/- 2.332, 14.018 +/- 6.081, and 14.082 +/- 1.670 %ID/g (mean +/- SD) at 10, 60, and 120 min after injection, respectively. By contrast, galactose-free (99m)Tc-MC accumulated faintly in the liver.


CONCLUSIONS
(99m)Tc-GMC specifically localized to the liver except for the kidneys in the mouse. GMC may be used to target the ASGP-R on the hepatocytes for nuclear imaging.
Kim
Eun-Mi
EM
Department of Nuclear Medicine, Wonkwang University School of Medicine, 344-2 Sinyong-dong, Iskan, Jellabuk-do, 570-711, Korea.
Jeong
Hwan-Jeong
HJ
Park
In-Kyu
IK
Cho
Chong-Su
CS
Kim
Chang-Guhn
CG
Bom
Hee-Seung
HS
D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D022781:Hepatocytes / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution
D037263:Asialoglycoprotein Receptor; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C498054:technetium 99m galactosyl-methylated chitosan; D048271:Chitosan