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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
Chemical name: | 99mTc-Hydrazinonicotinamide-galactosyl-chitosan | |
Abbreviated name: | 99mTc-HGC | |
Synonym: | ||
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 | |
Activation: | No | |
Studies: |
| Click on protein, nucleotide (RefSeq), and gene for more information about ASGP-R. |
Background
[PubMed]
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.
Synthesis
[PubMed]
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%.
Animal Studies
Rodents
[PubMed]
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.
References
- 1.
- Stockert R.J. The asialoglycoprotein receptor: relationships between structure, function, and expression. Physiol Rev. 1995;75(3):591–609. [PubMed: 7624395]
- 2.
- 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]
- 3.
- 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]
- 4.
- 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]
- 5.
- 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]
- PubMedLinks to PubMed
- Review (99m)Tc-Galactosyl-methylated chitosan.[Molecular Imaging and Contrast...]Review (99m)Tc-Galactosyl-methylated chitosan.Leung K. Molecular Imaging and Contrast Agent Database (MICAD). 2004
- Review (99m)Tc-Diethylenetriamine pentaacetic acid superparamagnetic iron oxide nanoparticles conjugated with lactobionic acid.[Molecular Imaging and Contrast...]Review (99m)Tc-Diethylenetriamine pentaacetic acid superparamagnetic iron oxide nanoparticles conjugated with lactobionic acid.Leung K. Molecular Imaging and Contrast Agent Database (MICAD). 2004
- Review (99m)Tc-Diethylenetriamine pentaacetic acid–lactosyl human serum albumin.[Molecular Imaging and Contrast...]Review (99m)Tc-Diethylenetriamine pentaacetic acid–lactosyl human serum albumin.Shan L. Molecular Imaging and Contrast Agent Database (MICAD). 2004
- Review [(99m)Tc]-diethylenetriaminepentaacetic acid-galactosyl human serum albumin.[Molecular Imaging and Contrast...]Review [(99m)Tc]-diethylenetriaminepentaacetic acid-galactosyl human serum albumin.Chopra A. Molecular Imaging and Contrast Agent Database (MICAD). 2004
- Hepatocyte-targeted nuclear imaging using 99mTc-galactosylated chitosan: conjugation, targeting, and biodistribution.[J Nucl Med. 2005]Hepatocyte-targeted nuclear imaging using 99mTc-galactosylated chitosan: conjugation, targeting, and biodistribution.Kim EM, Jeong HJ, Park IK, Cho CS, Kim CG, Bom HS. J Nucl Med. 2005 Jan; 46(1):141-5.
- 99mTc-Hydrazinonicotinamide-galactosyl-chitosan - Molecular Imaging and Contrast...99mTc-Hydrazinonicotinamide-galactosyl-chitosan - Molecular Imaging and Contrast Agent Database (MICAD)
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