본문 바로가기 주메뉴 바로가기
22대 대한민국 국회 국회정보길라잡이 국회의원검색
회원가입 로그인
HOME

정보검색

소장정보 검색

국회도서관 홈으로 정보검색 소장정보 검색

결과 내 검색

동의어 포함

고급검색

인명/단체명

저자정보 상세정보
인명/단체명을 입력하세요.

키워드

  • 대표어

  • 외국어

-

목차보기

Title Page

Abstract

Contents

List of Abbreviations 13

Chapter 1. Introduction 15

1. Cancer 15

A. Tumor 15

B. Cancerous Progression 16

2. Targeted Therapy of Cancer 19

3. Research Purposes 21

Chapter 2. Theoretical Background 24

1. Radiopharmaceuticals 24

2. Technetium and Rhenium in Radiopharmaceuticals 26

3. Development of Target Specific Radiopharmaceuticals 31

4. Peptide Receptors in Oncology 32

5. Design of Peptide-based Radiopharmaceuticals 37

6. Somatostatin Receptor Targeting 43

A. Lung Cancer 43

B. Somatostatin Analogue 44

C. Radiolabeled Somatostatin Analogues 47

7. Melanocortin-1 Receptor (MC1-R) Targeting 49

A. Melanoma 49

B. Melanocortin-1 Receptor (MC1-R) 53

C. Radiolabeled α-MSH Analogues 54

Chapter 3. Approaches and Experiments 57

1. Approaches 57

A. Synthesis of peptides 57

B. Characterization of peptide 61

C. Radiolabeling 62

D. Biological Evaluation 63

2. Experiments 64

A. Materials and Methods 64

B. Synthesis and Characterization of Peptides 65

C. Radiolabeling of Peptide with 99mTc and 188Re(이미지참조) 67

D. Preparation of Radiolabeled Peptides 68

E. In vitro Test 69

F. Biodistribution Studies 71

G. Radionuclide therapy of 188Re-N₂S₂-α-MSH(이미지참조) 72

H. Molecular Modeling 72

Chapter 4. Results and Discussion 74

1. Synthesis of Peptide 74

A. N₂S₂-Somatostatin 74

B. α-MSH Analogue 80

2. Radiolabeled-peptides with 99mTc and 188Re(이미지참조) 92

A. 99mTc-labeled Peptides(이미지참조) 92

B. 188Re-labeled Peptides(이미지참조) 96

3. Biodistribution Studies 110

A. 188Re-N₂S₂-Somatostatin(이미지참조) 110

B. 188Re-N₂S₂-α-MSH(이미지참조) 113

C. 188Re-N₂S₂-Glucose-α-MSH(이미지참조) 115

4. Radionuclide Therapy of 188Re-N₂S₂-α-MSH(이미지참조) 116

Tumor growth inhibition 116

Treatment Efficacy 117

Chapter 5. Conclusions 119

Somatostatin Analogue 119

α-MSH Analogues 120

References 123

초록 132

List of Tables

Table 1. Peptide library approached to discover tumor targeting peptides 21

Table 2. Characterization of various technetium-based pharmaceuticals with 5 coordination number 29

Table 3. Peptides for disease targeting 36

Table 4. Selected β-particle emitting radionuclides with therapeutic potential 42

Table 5. Frequency of histological types of lung cancer 43

Table 6. Presence of different somatostatin receptor (SSTR) subtypes in human tumor tissues 45

Table 7. Incidence rates of melanoma by race in the United States 50

Table 8. Death rates of melanoma by race in the United States 51

Table 9. Melanoma stages 52

Table 10. Evaluation method of radiolabeling yield and radiochemical purity of 99mTc-GH or 188Re-GH using tin layer chromatography(이미지참조) 68

Table 11. Tumour-to-blood ratio of 188Re-N₂S₂-somatostatin in Calu-6 bearing mice(이미지참조) 110

Table 12. Tumour-to-blood ratio of 188Re-N₂S₂-α-MSH in B16/F1 bearing mice(이미지참조) 113

List of Figures

Figure 1. Classification of tumor 15

Figure 2. Cancer, the process of growth 17

Figure 3. Schematic diagram of research processes 23

Figure 4. Imaging instrumentation for disease diagnosis 25

Figure 5. Periodic Table of the elements 28

Figure 6. Chemical formulas of selected technetium radiopharmaceuticals 30

Figure 7. Radiolabeled compounds for somatostatin receptor targeting 34

Figure 8. Concept for the development of target specific radiopharmaceuticals 39

Figure 9. Examples of covalent cyclizations 40

Figure 10. Structure of somatostatin analogues 47

Figure 11. Structure of chelator-conjugate octreotide 48

Figure 12. Melanocortin-1 receptor targeting for melanoma therapy 55

Figure 13. Structure of Re-CCMSH 56

Figure 14. Peptide synthesis using Fmoc strategy 58

Figure 15. Fmoc-solid phase peptide synthesis strategy 60

Figure 16. Scheme for N₂S₂-somatostatin synthesis using Fmoc strategy 75

Figure 17. Structure of N₂S₂-somatostatin 76

Figure 18. HPLC profile of N₂S₂-somatostatin 77

Figure 19. Mass analysis of N₂S₂-Somatostatin 78

Figure 20. Molecular modeling of N₂S₂-somatostatin 79

Figure 21. Scheme for N₂S₂-α-MSH synthesis using Fmoc strategy 81

Figure 22. Structure of N₂S₂-α-MSH 82

Figure 23. HPLC profile of N₂S₂-α-MSH 83

Figure 24. Mass analysis of N₂S₂-α-MSH 84

Figure 25. Molecular modeling of N₂S₂-α-MSH 85

Figure 26. Scheme for glucose linker synthesis 86

Figure 27. Scheme for N₂S₂-glucose-α-MSH synthesis using Fmoc strategy 88

Figure 28. Structure of N₂S₂-glucose-α-MSH 89

Figure 29. HPLC profile of N₂S₂-glucose-α-MSH 90

Figure 30. Mass analysis of N₂S₂-glucose-α-MSH 91

Figure 31. ITLC-SG pattern for 99mTc-GH Radiolabeling yield(%) ＝ 100% - % of Na99mTcO₄ - % of 99mTc-colloid(이미지참조) 93

Figure 32. HPLC profile of 99mTc-N₂S₂-somatostatin(이미지참조) 94

Figure 33. HPLC profile of 99mTc-N₂S₂-α-MSH(이미지참조) 95

Figure 34. ITLC-SG pattern for 188Re-GH (2 mg SnCl₂ · 2H₂O) Radiolabeling yield (%) ＝ 100% - % of Na188ReO₄ - % of 188Re-colloid(이미지참조) 97

Figure 35. ITLC-SG pattern for 188Re-GH (0.45 mg SnCl₂ · 2H₂O)(이미지참조) 98

Figure 36. Transchelation effect of 188Re-GH(이미지참조) 99

Figure 37. Radiolabeling of N₂S₂-somatostatin with 188Re(이미지참조) 100

Figure 38. HPLC profile of 188Re-N₂S₂-somatostatin(이미지참조) 101

Figure 39. Radiolabeling yield of 188Re-N₂S₂-Somatostatin with a different concentration(이미지참조) 102

Figure 40. Serum stability of 1188Re-N₂S₂-somatostatin(이미지참조) 103

Figure 41. Radiolabeling of N₂S₂-α-MSH with 188Re(이미지참조) 104

Figure 42. HPLC profile of 188Re-labeled α-MSH derivatives(이미지참조) 105

Figure 43. Radiolabeling yield of 188Re-N₂S₂-α-MSH with a different concentration(이미지참조) 106

Figure 44. Radiolabeling yield of 188Re-N₂S₂-glucose-α-MSH with a different concentration(이미지참조) 107

Figure 45. Serum stability of 188Re-labeled α-MSH derivatives(이미지참조) 109

Figure 46. Biodistribution of 188Re-N₂S₂-somatostatin in Calu-6 bearing mice(이미지참조) 112

Figure 47. Biodistribution of 188Re-N₂S₂-α-MSH in B16/F1 bearing mice(이미지참조) 114

Figure 48. Biodistribution of 188Re-N₂S₂-glucose-α-MSH in B16/F1 bearing mice(이미지참조) 115

Figure 49. Effects of 188Re-N₂S₂-α-MSH on the tumor growth of B16/F1 tumor bearing mice(이미지참조) 117

Figure 50. Effects of 188Re-N₂S₂-α-MSH on the survival rate of B16/F1 tumor bearing mice(이미지참조) 118

추천서가 (다양한 추천 자료를 만나보세요)

권호기사보기

권호기사 목록 테이블로 기사명, 저자명, 페이지, 원문, 기사목차 순으로 되어있습니다.
기사명 저자명 페이지 원문 기사목차

권호

기사명 원문보기 기사목차
닫기