A Novel Chelator Of Internal Contamination Of Radiostrontium

Objective: To develop novel CTS-EDTA nanoparticles, evaluate its pharmacokineticsand observe the chelate effect on the removal of polluted⁸⁹Sr²⁺in the mice.Methods: CTS-EDTA was synthesized by the N-acylation reaction of EDTA withchitosan （CTS） which has low molecular weight and high deacetylation degree. Thenanoparticle （CEC-Nano） was prepared by cross-linking CTS-EDTA by sodiumtripolyphosphate solution （TPP） with the ionotropic gelation method. The CEC-Nanolabeled with¹⁸F was administered by iv and ig respectively. The dynamic images wereacquired by Micro-PET in2hours after administration, these images were reconstructedin the form of OSEM3D, and then the regions of interesting （ROIs） were drawn forcalculating the metabolic curve and for evaluating the pharmacokinetics with DAS2.0software. The animal model of internal contamination of radiostrontium was establishedby intraperitoneal injection of0.1mL⁸⁹SrCl₂solution at radioactivity of3.7104Bq.The experimental animals were randomly divided into control group, instant treatmentgroup and preventive treatment group. In the control group and instant treatment group,the polluted animals were immediately intravenous injected with0.1mL of0.9%saltsolution and0.1mL of4mg/mL CEC-nano respectively, and in the preventivetreatment group, the animals were intravenous injected0.1mL of4mg/mL CEC-nanohalf an hour before contamination of radiostrontium. The images of ROIs indicating toradioactivity of⁸⁹Sr²⁺in mice were observed by Kodak In-Vivo Imaging Systems at5min,24h and48h after treatment, respectively. The radioactivity of collected urine andfeces of the mice were measured daily. The mice were sacrificed at48h after treatment,the radioactivity of the tissues and residual ash of whole body were measured.Results: The CTS-EDTA compound was synthesized successfully, which wasconfirmed by FT-IR and1H-NMR. The prepared CEC-Nano was a globular nanometerparticle with average diameter of162.2nm, which was determined by transmissionelectron microscopy and laser particle size analyzer. In pharmacokinetics experiments，the¹⁸F-CEC-Nano has low bioavailability with poor biological uptake after intragastric administration, its main distribute organs were liver and kidney, and its main excretionpathway was urinary system. The pharmacokinetic profiles of¹⁸F-CEC-Nano fit to thethree compartment model, and the total half-life was122.66min. The experiment ofdecorporation in vivo showed that the femur、skull and sternum were the main depositedorgans of⁸⁹Sr²⁺, the radioactivity of other organs was too low to statistical analysis. Itwas observed that radioactivity of collected urine in24h in the mice of the preventivetreatment group was obviously higher than that in other groups （p<0.05）, however, theradioactivity of collected feces has no differences in the three groups. The radioactivityof skull and sternum in the instant treatment group and preventive treatment group waslower compared to control （p<0.05）, additionally, the radioactivity of skull and sternumin the mice of the preventive treatment group was lower than that in the mice of theinstant treatment group （p<0.05）. The radioactivity in the femoral was no obviousdifferences among the three treated groups （p>0.05）. Compared to the control group, theradioactivity of residual ash of mouse body in the instant treatment group andpreventive treatment group was significantly lower （p<0.05）. The chelating efficiencyof CEC-Nano in preventive treatment group was higher than that in other groups.Conclusions: On the basis of previous work in our laboratory, the new CEC-Nanohas been prepared sucessfully. The CEC-Nano has low bioavailability with poorbiological uptake after intragastric administration, its main distribute organs were liverand kidney, and the main excretion pathway was urinary system. The pharmacokineticprofiles of¹⁸F-CEC-Nano fit to the three compartment model, and the total half-life was122.66min. The results of chelating experiment in vivo showed that the CEC-Nano haseffective decorporate and removal function when it was administrated beforecontamination of radiostrontium or immediately contamination of radiostrontium totreatment, and the pre-treatment was better. Further, the CEC-Nano has strongerdecorporate and removal effect on flat bone such as skull and sternum than that on thefemora. The CEC-Nano chelating role was played by increasing the exclusion amountof radioactive strontium in the urine.