ABSTRACT
OBJECTIVE: To investigate the biological character of new agent 153Sm-citrate-nano-Hydroxyapatite (nano-HA) in vitro and in vivo, and to explore a new radiopharmaceutical for the target therapy of bone metastasis cancer. METHODS: The nano-HA was synthesized by collosol-gelatum method, and evaluated by transmission electron microscopy (TEM) and X-ray diffraction (XRD). 153Sm was produced at a high specific activity and excellent radionuclidic purity, with which nano-HA was labeled by citrate transfer ligands in the best environment. By adopting the independent variable method, we also studied the optimally labeled condition and stability of 153Sm-citrate-nano-HA in vitro. And 153Sm-citrate-nano-HA was injected into normal rabbits for radio scanning performed. The cancer cell SMMC-7721 and MCF-7 cell lines were divided into two groups, and treated with nano-HA, 153Sm-citrate and 153Sm-citrate-nano-HA in vitro respectively, of which the cell survival rate was measured by MTT methods. RESULTS: Through the detections of TEM, XRD showed that nano-HA consisted of needle-like microcrystals. The label rate of 153Sm-citrate-nano-HA was more than 95%, and extremely stable in vitro. The radio scanning of normal rabbits showed the skeletal system to be clear, and other systems, for example liver, spleen and kidney, could also be seen. The cell culture experiments in vitro indicated that 153Sm-citrate-nano-HA strongly inhibited the proliferation of SMMC-7721 and MCF-7 cells. 153Sm-citrate-nano-HA's half effective inhibition concentrations were 1.89 mg/L and 0.094 mg/L respectively; nano-HA's half effective inhibition concentrations were 3. 31 mg/L and 0.52 mg/L respectively; 153Sm-citrate's half effective inhibition concentrations were 4. 32 mg/L and 0. 67 mg/L respectively. CONCLUSIONS: Sm-citrate-nano-HA shows fine biological properties, and is well worth for further researched and prepared as a promising potential radiopharmaceutical in nuclidic treatment for cancer bone metastases.
Subject(s)
Citrates/chemistry , Durapatite/chemistry , Radiopharmaceuticals/chemistry , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Microscopy, Electron, Transmission , Nanoparticles , Rabbits , Radioisotopes/chemistry , Samarium/chemistry , X-Ray DiffractionABSTRACT
Conditions for preparing Sn-EDTMP, Sn-DTPMP, Sn-TTHMP, Sn-HEDTMP and Sn-DTPA in aqueous solution in open air environments, and their in vitro properties including adsorption on hydroxyapatite (HA) and collagen (I) and binding to bovine serum albumin (BSA) were studied using (117m)Sn and 113Sn as tracers. Biodistributions of SnO2.xH2O.yEDTMP, SnO2.xH2O.yDTPMP, SnO2.xH2O.yTTHMP, SnO2.xH2O.yHEDTMP, SnO2.xH2O.yDTPA in normal mice were also tested. Based on the above experiments, the relationship between in vitro biochemical properties and biodistributions of these SnO2.xH2O.yLigands was investigated. The results show that Sn(IV)-Ligands are prone to hydrolysis into SnO2.xH2O.yLigands in aqueous solutions in open air environments, especially when the ligand is DTPA, when the molar ratio of metal to ligand is higher than 1:200, or when the pH of the solution is higher than 10. The in vitro experiments show that all of the SnO2.xH2O.yLigands bind strongly to BSA, and the binding percentages of SnO2.xH2O.yLigands to BSA are much higher than those of the corresponding Sn(IV)-Ligands. The biodistribution data indicate that all of the SnO2.xH2O.yLigands locate mainly in bone with little uptake in liver. When the binding percentages of SnO2.xH2O.yLigands to BSA are similar, those SnO2.xH2O.yLigands with higher adsorption on HA and collagen (I) undergo lower liver uptake.
