Polysaccharide Radioisotopic Labeling and Its Application in Pharmacokinetics Study In Vivo
ZHENG Zi-ming1, ZHANG Yu1, ZHANG Qi-lin1, LUO Li1, PAN Xiang-lin1, WANG Kai-ping2*
1. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; 2. Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China
Abstract：Polysaccharides were widely developed as drugs or health care products due to their good pharmacological activities and low side effects. With the research on the physicochemical properties of polysaccharides, polysaccharides as biomaterials were gradually used in the development of new preparations. However, compared with the researches of polysaccharides on pharmacological activities and as biomaterials, their pharmacokinetics studies in vivo were obviously insufficient, which seriously limited the development of polysaccharides as drugs and biomaterials. At present, radioisotope labeling has become an important method for the study of polysaccharide pharmacokinetics in vivo. This paper summarizes various radioisotopes used for polysaccharide labeling, and analyzes the characteristics of different radioisotopes in the study of polysaccharide pharmacokinetics in vivo. Moreover, the factors influencing the pharmacokinetics of polysaccharides are analyzed, and the application based on the pharmacokinetics characteristics of polysaccharides in vivo is discussed. The in-depth study on the pharmacokinetics of polysaccharides in vivo could provide important guidance for the development of polysaccharides as drugs and biomaterials.
郑子明, 张玉, 张琪琳, 罗立, 潘祥林, 王凯平. 多糖放射性同位素标记及其体内药动学应用的研究进展[J]. 中国药学杂志, 2022, 57(8): 599-604.
ZHENG Zi-ming, ZHANG Yu, ZHANG Qi-lin, LUO Li, PAN Xiang-lin, WANG Kai-ping. Polysaccharide Radioisotopic Labeling and Its Application in Pharmacokinetics Study In Vivo. Chinese Pharmaceutical Journal, 2022, 57(8): 599-604.
WANG Y, FAN H H, Quality control strategies and research progress in quality control technology of polysaccharide biochemical drugs[J]. Chin Pharm J (中国药学杂志), 2021, 56(1):8-12.
[2]
ZHANG J, LIU Y, TANG Q, et al. Polysaccharide of ganoderma and its bioactivities[J]. Adv Exp Med Biol, 2019, 1181:107-134.
[3]
YU Y, SHEN M, SONG Q, et al. Biological activities and pharmaceutical applications of polysaccharide from natural resources: A review[J]. Carbohydr Polym, 2018, 183:91-101.
[4]
ZHANG Q, DU Z, ZHANG Y, et al. Apoptosis induction activity of polysaccharide from Lentinus edodes in H22-bearing mice through ROS-mediated mitochondrial pathway and inhibition of tubulin polymerization[J]. Food Nutr Res, 2020, 64:4364.
[5]
WANG K, XU J, LIU Y, et al. Self-assembled Angelica sinensis polysaccharide nanoparticles with an instinctive liver-targeting ability as a drug carrier for acute alcoholic liver damage protection[J]. Int J Pharm, 2020, 577:118996.
[6]
DONG W, HAN B, SHAO K, et al. Effects of molecular weights on the absorption, distribution and urinary excretion of intraperitoneally administrated carboxymethyl chitosan in rats[J]. J Mater Sci Mater Med, 2012, 23(12):2945-2952.
[7]
ZHANG Y, ZHENG Z, YANG X, et al. A sensitive and rapid radiolabelling method for the in vivo pharmacokinetic study of lentinan[J]. Food Funct, 2018, 9(6):3114-3125.
[8]
LAZNICEK M, LAZNIEKOVA A, COZIKOVA D, et al. Preclinical pharmacokinetics of radiolabelled hyaluronan[J]. Pharmacol Rep, 2012, 64(2):428-437.
[9]
BALOGH L, POLYAK A, MATHE D, et al. Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs[J]. J Agric Food Chem, 2008, 56(22):10582-10593.
[10]
ZHANG Y, ZHOU T, LUO L, et al. Pharmacokinetics, biodistribution and receptor mediated endocytosis of a natural Angelica sinensis polysaccharide[J]. Artif Cells Nanomed Biotechnol, 2018, 46(suppl 1):254-263.
[11]
CHEN J, PANG W, KAN Y, et al. Structure of a pectic polysaccharide from Pseudostellaria heterophylla and stimulating insulin secretion of INS-1 cell and distributing in rats by oral[J]. Int J Biol Macromol, 2018, 106:456-463.
[12]
KELLAWAY I W, SEALE L, SPENCER P S, The in vitro characterization and biostability of 99mTc-dextran and its accumulation within the inflamed paws of adjuvant-induced arthritic rats[J]. Pharm Res, 1995, 12(4):588-593.
[13]
MANG′ERA K, KRZYZELEWSKI M, GREAVES S, et al. Molecular-size fractionation of pentastarch, radiolabelling with 99mTc, and evaluation of biological behaviour in mice[J]. Nucl Med Commun, 2005, 26(4):375-381.
[14]
KIM E M, JEONG H J, KIM S L, et al. Asialoglycoprotein-receptor-targeted hepatocyte imaging using 99mTc galactosylated chitosan[J]. Nucl Med Biol, 2006, 33(4):529-534.
[15]
KIM E M, JEONG H J, PARK I K, et al. Hepatocyte-targeted nuclear imaging using 99mTc-galactosylated chitosan: conjugation, targeting, and biodistribution[J]. J Nucl Med, 2005, 46(1):141-145.
[16]
SOBAL G, VELUSAMY K, KOSIK S, et al. Preclinical evaluation of (99m)Tc labeled chondroitin sulfate for monitoring of cartilage degeneration in osteoarthritis[J]. Nucl Med Biol, 2016, 43(6):339-346.
[17]
SAFFARI H, PETERSON K A, LEIFERMAN K M, et al. Oral administration of (99m) technetium-labeled heparin in eosinophilic esophagitis[J]. Mayo Clin Proc, 2020, 95(3):449-458.
[18]
CHAUVIERRE C, AID-LAUNAIS R, AERTS J, et al. Pharmaceutical development and safety evaluation of a GMP-grade fucoidan for molecular diagnosis of cardiovascular diseases[J]. Mar Drugs, 2019, 17(12):699.
[19]
VIGNE J, COGNET T, GUEDJ K, et al. Early detection of localized immunity in experimental autoimmune myocarditis using [(99m)Tc] fucoidan SPECT[J]. Mol Imaging Biol, 2020, 22(3):643-652.
[20]
TANAKA T, FUJISHIMA Y, HANANO S, et al. Intracellular disposition of polysaccharides in rat liver parenchymal and nonparenchymal cells[J]. Int J Pharm, 2004, 286(1-2):9-17.
[21]
TANAKA T, FUJISHIMA Y, HANANO S, et al. Cellular disposition of arabinogalactan in primary cultured rat hepatocytes[J]. Eur J Pharm Sci, 2004, 22(5):435-444.
[22]
TANAKA T, HANANO S, FUJISHIMA Y, et al. Uptake of pullulan in cultured rat liver parenchymal cells[J]. Biol Pharm Bull, 2005, 28(3):560-562.
[23]
KANEO Y, TANAKA T, NAKANO T, et al. Evidence for receptor-mediated hepatic uptake of pullulan in rats[J]. J Controlled Release, 2001, 70(3):365-373.
[24]
JIANG Q Y, Study on absorption of hyaluronic acid after oral administration and its mechanism[D]. Shandong: Ocean Univ of Chain (中国海洋大学), 2006.
[25]
GAO Q P, CHEN H Q, WANG K, et al. Studies on the absorpation , distribution and clearance of tremella polysaccharide in rats[J]. Chin Pharm J (中国药学杂志), 2002, 37(3):205-208.
[26]
YOSHIDA M, ROTH RI, GRUNFELD C, et al. Soluble (1→3)-beta-D-glucan purified from Candida albicans: biologic effects and distribution in blood and organs in rabbits[J]. J Lab Clin Med, 1996, 128(1):103-114.
[27]
STIMPSON S A, ESSER R E, CROMARTIE W J, et al. Comparison of in vivo degradation of 125I-labeled peptidoglycan-polysaccharide fragments from group A and group D streptococci[J]. Infect Immun, 1986, 52(2):390-396.
[28]
LENDVAI N, CASADEVALL A, LIANG Z, et al. Effect of immune mechanisms on the pharmacokinetics and organ distribution of cryptococcal polysaccharide[J]. J Infect Dis, 1998, 177(6):1647-1659.
[29]
HWANG H, KIM K I, KWON J, et al. (131)I-labeled chitosan hydrogels for radioembolization: A preclinical study in small animals[J]. Nucl Med Biol, 2017, 52:16-23.
[30]
YANG X, WANG J, DING Z, et al. Dual-radiolabelling of an injectable hyaluronan-tyramine-bisphosphonate hybrid gel for in vitro and in vivo tracking[J]. Carbohydr Polym, 2020, 231:115652.
[31]
O′HARA Y, Fate of lentinan (antitumor polysaccharide) I: fate of lentinan in mice, rats, and dogs [J]. J Toxicol Sci, 1980, 5(Suppl):59-72.
[32]
KOYAMA Y, MIYAGAWA T, KAWAIDE A, et al. Receptor-mediated absorption of high molecular weight dextrans from intestinal tract[J]. J Control Release, 2015, 41(3):171-176.
[33]
ZHANG L P, WEN S W, ZHOU Y F, et al. Preliminary study on the absorption and metabolism of 3H-mannan in mice[J]. J Northeast Norm Univ (东北师大学报), 1994, (1):54-57.
[34]
OE M, MITSUGI K, ODANAKA W, et al. Dietary hyaluronic acid migrates into the skin of rats[J]. Sci World J, 2014, 2014:378024.
[35]
SVANOVSKY E, VELEBNY V, LAZNICKOVA A, et al. The effect of molecular weight on the biodistribution of hyaluronic acid radiolabeled with 111In after intravenous administration to rats[J]. Eur J Drug Metab Pharmacokinet, 2008, 33(3):149-157.
[36]
DUHERON V, MOREAU M, COLLIN B, et al. Dual labeling of lipopolysaccharides for SPECT-CT imaging and fluorescence microscopy[J]. ACS Chem Biol, 2014, 9(3):656-662.
[37]
ISIBASI A, JIMENEZ E, KUMATE J, Clearance and tissue distribution of intravenously injected Salmonella typhi polysaccharide in rabbits[J]. Infect Immun, 1983, 42(3):949-954.
[38]
ZHANG Y, ZHOU T, WANG H, et al. Structural characterization and in vitro antitumor activity of an acidic polysaccharide from Angelica sinensis (Oliv.) Diels[J]. Carbohydr Polym, 2016, 147:401-408.
[39]
XU S, PING Z, XU X, et al. Changes in shape and size of the stiff branched beta-glucan in dimethlysulfoxide/water solutions[J]. Carbohydr Polym, 2016, 138:86-93.
[40]
HAGHIGHATAFSHAR M, GHEISARI F, GHAEDIAN T, Importance of heparin provocation and SPECT/CT in detecting obscure gastrointestinal bleeding on 99mTc-RBC scintigraphy: a case report[J]. Med (Baltimore), 2015, 94(34):e1325.
[41]
YAMAGUCHI A, HANAOKA H, PIRMETTIS I, et al. Injection site radioactivity of (99m)Tc-labeled mannosylated dextran for sentinel lymph node mapping[J]. Mol Pharm, 2015, 12(2):514-519.
[42]
CAO XS, YANG GR, CONG BB, et al. The lymphatic drainage pattern of internal mammary sentinel lymph node identified by small particle radiotracer (99mTc-Dextran 40) in breast[J]. Cancer Res Treat, 2019, 51(2):483-492.
[43]
BANZATO A, RONDINA M, MELENDEZ-ALAFORT L, et al. Biodistribution imaging of a paclitaxel-hyaluronan bioconjugate[J]. Nucl Med Biol, 2009, 36(5):525-533.
[44]
ZHAO Q, TOLMACHEV V, CARLSSON J, et al. Effects of dextranation on the pharmacokinetics of short peptides, A PET study on mEGF[J]. Bioconjug Chem, 1999, 10(6):938-946.
[45]
HAGERT C, SIITONEN R, LI XG, et al. Rapid spread of mannan to the immune system, skin and joints within 6 hours after local exposure[J]. Clin Exp Immunol, 2019, 196(3):383-391.
[46]
LI XG, HAGERT C, SIITONEN R, et al. (18)F-labeling of mannan for inflammation research with positron emission tomography[J]. ACS Med Chem Lett, 2016, 7(9):826-830.
[47]
KUHNAST B, EL HADRI A, BOISGARD R, et al. Synthesis, radiolabeling with fluorine-18 and preliminary in vivo evaluation of a heparan sulphate mimetic as potent angiogenesis and heparanase inhibitor for cancer applications[J]. Org Biomol Chem, 2016, 14(6):1915-1920.
[48]
KUNTNER C, WANEK T, HOFFER M, et al. Radiosynthesis and assessment of ocular pharmacokinetics of (124)I-labeled chitosan in rabbits using small-animal PET[J]. Mol Imaging Biol, 2011, 13(2):222-226.
[49]
ISRAEL I, FLURI F, SCHADT F, et al. Positron emission tomography and autoradiography imaging of P-selectin activation using 68Ga-fucoidan in photothrombotic stroke[J]. Curr Neurovasc Res, 2018, 15(1):55-62.
2022, Vol. 57 
