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Title page
Contents
Abbreviation 10
Abstract 11
I. Introduction 13
II. Materials and methods 18
1. Materials 18
2. Methods 19
2.1. Synthesis of rac-2,3-dimercaptosuccinic acid 19
2.1.1. rac-Bis(thioacetyl) succinic acids 19
2.1.2. rac-2,3-dimercaptosuccinic acids 19
2.2. Preparation of 188Re(V)-DMSA(이미지참조) complexes 20
2.2.1. 188Re(V)-meso-DMSA(이미지참조) complex 20
2.2.2. 188Re(V)-rac-DMSA(이미지참조) complex 21
2.3. Chromatographic analysis of 188Re(V)-DMSA(이미지참조) complexes 21
2.4. Biochemical characterizations of 188Re(V)-DMSA(이미지참조) complexes 23
2.4.1. in vitro stability 23
2.4.2. Lipophilicity 23
2.4.3. Bindability to protein 24
2.5. Organ distribution of 188Re(V)-DMSA(이미지참조) complexes in nude mouse bearing PC-12 24
2.5.1. Cell culture and tumor implantation 24
2.5.2. Organ distribution studies 25
2.6. Gamma camera image with 188Re(V)-DMSA(이미지참조) complexes in nude mouse bearing PC-I2 26
III. Results 27
1. Synthesis of rac-2,3-dimercaptosuccinic acid 27
2. Preparation of 188Re-DMSA(이미지참조) complexes 27
2.1. 188Re(V)-meso-DMSA(이미지참조) complexes 27
2.2. 188Re(V)-rac-DMSA(이미지참조) complexes 28
3. Chromatographic analysis of 188Re(V)-DMSA(이미지참조) complexes 35
4. Biochemical characterizations of 188Re(V)-DMSA(이미지참조) complexes 41
5. Organ distribution of 188Re(V)-DMSA(이미지참조) complexes in nude mouse bearing PC-12 44
6. Gamma camera Image with 188Re(V)-DMSA(이미지참조) complexes in nude mouse bearing PC-12 49
IV. Discussion 53
V. Conclusion 57
VI. Reference 59
Abstract in Korean 64
Table 1. The optimal conditions for the preparation of 188Re(V)-DMSA(이미지참조) complexes 38
Table 2. Distribution between organic and aqueous phase and protein bindability of 188Re(V)-DMSA(이미지참조) complexes 43
Table 3. Biodistribution of 188Re-meso-DMSA(이미지참조) in nude mouse bearing PC-12 45
Table 4. Biodistribution of 188Re-rac-DMSA(이미지참조) in nude mouse bearing PC-12 47
Table 5. Organ per tissue ratios of 188Re(V)-DMSA(이미지참조) complexes 50
Figure 1. Production and decay mechanisms of 188Re(이미지참조) in generator system. 13
Figure 2. The chemical structure of DMSA. 14
Figure 3. Synthetic scheme of diastereomeric DMSA. 15
Figure 4. Synthetic scheme of diastereomeric 188Re(V)-DMSA(이미지참조) complexes. 22
Figure 5. Effect of MBS concentration on the yield of 188Re(V)-meso-DMSA(이미지참조). 29
Figure 6. Effect of 2,3-meso-DMSA concentration on the yield of 188Re-meso-DMSA(이미지참조). 30
Figure 7. Effect of pH on the yield of 188Re(V)-meso-DMSA(이미지참조). 31
Figure 8. Effect of MBS concentration on the yield of 188Re(V)-rac-DMSA(이미지참조). 32
Figure 9. Effect of rac-2,3-DMSA concentration on the yield of 188Re(V)-rac-DMSA(이미지참조). 33
Figure 10. Effect of pH on the yield of 188Re(V)-rac-DMSA(이미지참조). 34
Figure 11. Radiochromatogram of 188Re(V)-meso-DMSA(이미지참조). 36
Figure 12. Radiochromatogram of 188Re(V)-rac-DMSA(이미지참조). 37
Figure 13. HPLC chromatogram of 188Re(V)-meso-DMSA(이미지참조). 39
Figure 14. HPLC chromatogram of 188Re(V)-rac-DMSA(이미지참조). 40
Figure 15. in vitro stability test of 188Re(V)-DMSA complexes(이미지참조). 42
Figure 16. Biodistribution of 188Re(V)-meso-DMSA(이미지참조) in nude mouse bearing PC-12. 46
Figure 17. Biodistribution of 188Re(V)-rac-DMSA(이미지참조) in nude mouse bearing PC-12. 48
Figure 18. Gamma camera image of 188Re(V)-meso-DMSA(이미지참조) in nude mouse bearing PC-12. (The arrows indicate the tumor region) 51
Figure 19. Gamma camera image of 188Re(V)-rac-DMSA(이미지참조) in nude mouse bearing PC-12. (The arrows indicate the tumor region) 52
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