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A New Nano-chelating Agent To 89Sr

Posted on:2010-07-12Degree:MasterType:Thesis
Country:ChinaCandidate:L Z ZhangFull Text:PDF
GTID:2144360275959461Subject:Radiation Medicine
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Objective:To prepare CTS-EDTA(CEC) and CTS-EDTA-Nano(CEC-Nano) and investigate their effects of chelating Sr2+ in vitro and in vivo, and so provide theoratical and experiment basis for developing a new chelator to radionuclide 89Sr.Methods:The insoluble high molecular weight CTS-EDTA compound was synthesized by N-acylation reaction, and its chelating ability to Sr2+ was compared with CTS by atomic absorption spectrometry. For being satisfied with the preparation of new nano-chelating agent, the chitosan's degree of deacetylation (DD) was elevated with sodium hydroxide eluting and the high molecular weight CTS was cut down by radiolysis of 60Coγirradiation. The CTS-EDTA nanoparticles were prepared by ion cross-linking method, and its diameter as well as appearance was measured by Laser Particle Sizer, transmission and scanning eletron microscopy. The FITC was labeled to CTS-EDTA nanoparticles by the reaction between the isothiocyanate group of fluorescein isothiocyanate(FITC) and amino-group on the CTS-EDTA nanoparticles. Its capability of penetrating through cellular membrane was observed by Laser confocal microscopy. The chelating ability to 89Sr2+of CEC-Nano was compared with CEC and EDTA-Na2 in vitro by thin-layer chromatography. In addition, the chelating ability of CEC-Nano to 89Sr in vivo was investigated by animal experiment, which was compared with CEC and EDTA-Na2 .Results:The new CTS-EDTA compound was synthesized successfully, which was identified with FT-IR and 1H-NMR spectrum. The chelating efficiency of high molecular weight CTS-EDTA was above 80% in 10min, however, CTS was almost the same as control. After sodium hydroxide eluting, the CTS's degree of deacetylation(DD) was increased from 64.79% to 96.65% determined by linear potentiometric titration. After irradiated with 200kGy 60Coγrays, the molecular weight of CTS was decreased from 1850kDa to 2.5kDa measured by Ubbelohde Viscometer, and the circular main chain of chitosan was remained identified by FT-IR spectrum. The new CTS-EDTA with low molecular weight and high degree of deacetylation was qualified with preparing a new nano-chelator. The new nanoparticles (CEC-Nano) was spherical with uniform size, and the mean diameter was about 5.35±0.31nm (PDI=0.385). The new CEC-Nano could pass through the membrane and disperse in cytoplasm and cytoblast by observing the FITC-CEC-Nano probe. In vitro, the chelating efficiency of CEC-Nano, CEC and EDTA-Na2 were 90.50±5.07%, 84.05±3.08% and 57.24±3.37% respectively, the chelating ability of CEC-Nano was stronger than traditional chelator EDTA-Na2 significantly, evev though there was no significant difference between CEC-Nano and CEC. In vivo, it was also demonstrated that CEC-Nano had stronger chelating effect to 89Sr compared with traditional chelator EDTA-Na2, the excretion efficiency of CEC-Nano, CEC and EDTA-Na2 from digestive canal and urinary system were 42.52%, 37.64% and 0.20% respectively. Expecially compared with control group, injecting drug within 48 hours, the excretion efficiency of CEC-Nano, CEC and EDTA-Na2 from femoral bone had increased to 28.60%, 22.64% and 0.82% respectively, although there was no significant difference between CEC-Nano and CEC.Conclusion:A new chelator CEC-Nano has been developed successfully. It was demonstrated that the new chelator CEC-Nano had stronger chelating effect to radionuclide strontium than the traditional chelator EDTA-Na2, although there was no significant difference between CEC-Nano and CEC.
Keywords/Search Tags:chitosan(CTS), ethylenedinitrolotetraaceticacid(EDTA), CEC, CEC-Nano, chelator
PDF Full Text Request
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