| Objective:1. To develop 125I- 103Pd hybrid radioactive seeds, and to observe the killing effects and the tumor-inhibitory action of 125I- 103Pd hybrid radioactive seeds, by comparing with 125I and 103Pd radioactive seeds.2. To investigate the killing mechanism of 125I-103Pd seeds, by comparing with 125I and 103Pd radioactive seeds on tumor cells apoptosis, proliferation and metabolism.Method:1.125I- 103Pd hybrid radioactive seeds was developed by using chemical plating method, and the homogenicity of the seed was estimated by nuclide autograph and the measurement of nuclide seed activity.2. Cytological test:4 kind of lung cancer cells including A549, GLC-82,95D and H460 cells were chosen for tumor cell killing test, cell apoptosis test and cell proliferation test, in order to compare the effects of 125I- 103Pd seeds with 125I and 103Pd seeds on tumor cell growth in vitro.3. Seed implanting therapeutic test:the mouse models of transplanted tumors were built and the tumor-inhibitory action was compared between 125I- 103Pd,125I and 103Pd seeds.4. Molecular imaging test:tracer agents including 18F-FDG,18F-FLT and 11C-CH were adopted for PET examination on A549 and 95D tumor models, to learn about the effects of 125I- 103Pd,125I and 103Pd seeds on tumor cell metabolism and proliferation, in order to investigate the the killing mechanism of 125I- 103Pd seed on tumor cells.Result:1. Nuclide autograph and the measurement of nuclide seed activity indicated that, 125I- 103Pd seed was successfully developed, and thehomogenicity of the seed was reliable;2. In vitro cell killing test in 48 hours showed that,103Pd seed was the most effective, while 125I- 103Pd seed was more effective than 125I seed. The killing ranges of the three kind of radioactive seeds were of no significant difference, and tumor cells around radioactive seeds in a range of about 2 to 3 lengths of a seed were inhibited obviously。3. Cell apoptosis test indicated that, under 2Gy irradiation, no obvious difference in A549 cell apoptosis was observed among 125I- 103Pd,125I and 103Pd seeds (P>0.05). While under 2Gy irradiation,103Pd seed could induce more 95D cells to apoptosis and death than 125I-103Pd and 125I seeds (P<0.05), no difference was found between 25I- 103Pd and 125I seeds (P>0.05). Under 4Gy irradiation, as regard to both A549 and 95D cells, 125I- 103Pd seed was more effective in inducing tumor cell to apoptosis than 125I and 103Pd seeds did, while 103Pd seed could induce more tumor cells to death than 125I-103Pd and 125I seeds did.4. Tumor cell proliferation test in vitro showed that:From day 1 to day 4,103Pd seed was much more effective in cell growth inhibition than 125I- 103Pd and 125I seeds(P<0.05); From day 5 to day 7,125I- 103Pd and 103Pd seeds were identical in cell growth inhibition (P>0.05). While 125I seed was relatively the weakest radioactive seed in whole observation period (P<0.05);5. Seed implanting test in transplanted tumors showed that, 125I- 103Pd seed was the most effective in tumor inhibition, while 103Pd and 125I seeds were identical;6. PET-CT of A549 tumor models indicated that,125I- 103Pd,125I and 103Pd seeds could obviously inhibit A549 cells metabolism in glucose and nucleotide. As to glucose metabolism,103Pd seed is the more powerful than 125I-103Pd and 125I seeds, while 125I seeds is the weakest among the three kind of radioactive seeds. In the early observation time,103Pd seed was the most effective in the inhibition of the nucleotide metabolism, while 125I- 103Pd seed was the most powerful in the mid-and-later observation time; 125I seed was the weakest in the early observation time, while it was as effective as 103Pd seed in the mid-and-later observation time. The tendency of glucose metabolism is concordant to nucleotide metabolism, while the uptake value descended gradually along with the time of irradiation.7. PET-CT of 95D tumor models indicated that,125I- 103Pd was more effective than 125I seeds to inhibit cell metabolism in glucose and nucleotide. However, the tendency of glucose metabolism is inconcordant to nucleotide metabolism:the uptake value of glucose metabolismdescended gradually, while nucleotide metabolism was of little change in mid to late time of irradiation。8. The influence of 125I- 103Pd,125I and 103Pd seeds on the phospholipid metabolism of tumor cell were obvious. However, no difference was found among the 3 radioactive seed groups.Conclusion:1. The manufacture of 125I- 103Pd hybrid radioactive seed is possible, the homogenicity of the seed is reliable;2.125I- 103Pd,125I and 103Pd seeds are of no difference in effective killing range.3.125I seeds mainly induce tumor cells to apoptosis, and 10 Pd seeds mainly kill tumor cells directly, while 125I- 103Pd seeds may combine the character of the two nuclide.4. In tumor-inhibitory action,125I- 103Pd seed is more effective than 103Pd and 125I seeds, while 103Pd seed is comparable with 125I seed.5.125I- 103Pd,125I and 103Pd seeds can influence tumor cell metabolism in glucose, nucleotide and phospholipid. However, 125I- 103Pd seed is more powerful in inhibiting the nucleotide metabolism, than 125I and 103Pd seeds; Nucleotide metabolism could better reflect the tumor-inhibitory effect of radioactive seeds.
|
PDF Full Text Request