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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: December 2, 2009.

Chemical name:99mTc-Hydrazinonicotinamide-galactosyl-chitosan
Abbreviated name:99mTc-HGC
Agent category:Compound
Target:Asialoglycoprotein receptors (ASGP-Rs)
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), gamma planar imaging
Source of signal/contrast:99mTc
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about ASGP-R.



Asialoglycoprotein (ASGP) is specifically taken into mammalian hepatocytes by binding to ASGP receptors (ASGP-Rs) (1). The galactosyl moiety of ASGP is recognized on the surface of hepatocytes and is bound by ASGP-R. The ASGP–ASGP-R complex on the cell surface is subsequently taken into cytoplasm by endocytosis and transferred to lysosomes. ASGP-R is then dissociated from ASGP and recycled to the cell surface. ASGP is degraded in the lysosomes and excreted into the bile. The number of ASGP-Rs on the hepatocytes of individuals with liver disease decreases and is thus considered a good indicator for the evaluation of liver function. Because ASGP-R recognizes galactose, 99mTc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) (2, 3) and 99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) (4) are ASGP-R probes that accumulate specifically in the liver and are used for liver scintigraphy to determine liver mass and function. Chitosan is a linear polysaccharide composed of D-glucosamine and N-acetylglucosamine subunits with numerous amine groups of D-glucosamine for ligand conjugation. Kim et al. (5) conjugated hydrazinonicotinamide (HYNIC) and galactose (via lactobionic acid) to deacetylate chitosan for radiolabeling with 99mTc to form 99mTc-HYNIC-galactosyl-chitosan (99mTc-HGC) for imaging ASGP-R expression in the liver.



Deacetylated chitosan (5 kDa) was incubated with lactobionic acid, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride, and N-hydroxysuccinimide for 48 h at room temperature (5). The resulting galactosylated chitosan (GC) was purified with dialysis and incubated with 3 M excess succinimidyl HYNIC in 0.2 M borate buffer (pH 8.2) for 5 h at room temperature. HYNIC-GC (HGC) was isolated with dialysis. HGC (200 µg) was incubated with 74 MBq (2 mCi) 99mTc-sodium pertechnetate, tricine, and stannous chloride for 30 min at room temperature. 99mTc-HGC conjugates were isolated with column chromatography with >94% labeling efficiency. 99mTc-HGC conjugates were stable in saline up to 6 h. The amount of galactose in GC was 7 mol% and in HGC was 3 mol%.

In Vitro Studies: Testing in Cells and Tissues


No publication is currently available

Animal Studies



Kim et al. (5) performed ex vivo biodistribution studies in normal mice (n = 3/group) after intravenous injection of 99mTc-HGC at 10, 60, and 120 min. The initial tracer accumulation in the liver was 13.2% injected dose per gram (ID/g) at 10 min, 16.1% ID/g at 60 min, and 16.6% ID/g at 120 min after injection. The kidneys had the highest accumulation with 32.2%, 25.6%, and 23.3% ID/g at these time points, respectively. 99mTc-HGC was largely cleared by the kidneys. The stomach, intestine, heart, lung, muscle, blood, and spleen all showed relatively low accumulation. Single-photon emission computed tomography scintigraphic imaging was performed in mice after intravenous injection of 2.8 MBq (0.075 mCi) 99mTc-HGC at 10, 30, 60, and 120 min after injection. High accumulation was observed in the liver and kidneys within a few minutes after injection. The urinary bladder was also highly visualized. Co-injection of 0.05 mmol galactose with 99mTc-HGC greatly reduced the hepatic radioactivity with minimal effect in the kidneys. Injection of 99mTc-HYNIC-chitosan (non-galactosylated) showed high accumulation in the kidneys and urinary bladder with low radioactivity in the liver.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.


Stockert R.J. The asialoglycoprotein receptor: relationships between structure, function, and expression. Physiol Rev. 1995;75(3):591–609. [PubMed: 7624395]
Kwon A.H., Ha-Kawa S.K., Uetsuji S., Kamiyama Y., Tanaka Y. Use of technetium 99m diethylenetriamine-pentaacetic acid-galactosyl-human serum albumin liver scintigraphy in the evaluation of preoperative and postoperative hepatic functional reserve for hepatectomy. Surgery. 1995;117(4):429–34. [PubMed: 7716725]
Wu J., Ishikawa N., Takeda T., Tanaka Y., Pan X.Q., Sato M., Todoroki T., Hatakeyama R., Itai Y. The functional hepatic volume assessed by 99mTc-GSA hepatic scintigraphy. Ann Nucl Med. 1995;9(4):229–35. [PubMed: 8770291]
Vera D.R., Stadalnik R.C., Krohn K.A. Technetium-99m galactosyl-neoglycoalbumin: preparation and preclinical studies. J Nucl Med. 1985;26(10):1157–67. [PubMed: 4045560]
Kim E.M., Jeong H.J., Kim S.L., Sohn M.H., Nah J.W., Bom H.S., Park I.K., Cho C.S. Asialoglycoprotein-receptor-targeted hepatocyte imaging using 99mTc galactosylated chitosan. Nucl Med Biol. 2006;33(4):529–34. [PubMed: 16720245]


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