초록 ▼

○ 테라그노시스 의약품 개발 기초기술 확립
- 생분해입자에 방사성동위원소 표지 최적화함
- RGD 등 신생혈관추적 바이오마커 방사선표지 기술 개발함
- 골드나노입자 표면 개질 및 골드/철/고분자나노입자 방사성동위원소 표지 기술 개발함
- 줄기/면역세포에 방사성동위원소 표적 리포터유전자 이입기술 개발함

○ 테라그노시스 의약품 합성기술 최적화
- 방사선 생분해입자의 생체영상 최적화 및 치료효과 평가함
- 테라그노시스용 방사선표지 RGD 생체영상 및 치료효과 평가함
- 방사성동위원소 및

○ 테라그노시스 의약품 개발 기초기술 확립
- 생분해입자에 방사성동위원소 표지 최적화함
- RGD 등 신생혈관추적 바이오마커 방사선표지 기술 개발함
- 골드나노입자 표면 개질 및 골드/철/고분자나노입자 방사성동위원소 표지 기술 개발함
- 줄기/면역세포에 방사성동위원소 표적 리포터유전자 이입기술 개발함

○ 테라그노시스 의약품 합성기술 최적화
- 방사선 생분해입자의 생체영상 최적화 및 치료효과 평가함
- 테라그노시스용 방사선표지 RGD 생체영상 및 치료효과 평가함
- 방사성동위원소 및 리간드 표지 골드/철/고분자나노입자 영상 평가함
- 치료용 줄기/면역세포에 생체 분자영상 추적기술 최적화함

○ 테라그노시스 의약품 치료/영상 평가 및 임상 적용 후보 도출
- 종양 이중타겟 방사성생분해 입자 임상 후보물질 도출함
- 방사선 나노 테라그노스틱 다중영상 시스템 개발함
- 방사성표지 치료줄기/면역세포 영상추적 융합응용 임상적용 기술 도출함
- 후보물질 최적화 및 비임상 시험함


( 출처 : 보고서 요약서 3p )

Abstract ▼

Purpose&Contents
To develop personalized medicine which decreases side effects and enhances treatment effects in incurable disease, radiolabeled nano drug transmitters or cell therapeutic medicines makes imaging or radiotherapy possible simultaneously. This leads to the development and analysis o

Purpose&Contents
To develop personalized medicine which decreases side effects and enhances treatment effects in incurable disease, radiolabeled nano drug transmitters or cell therapeutic medicines makes imaging or radiotherapy possible simultaneously. This leads to the development and analysis of technology and medicine which make the treatment and biomonitoring possible simultaneously based on radio-theragnosis generic technology development.

Results
1. Radio-theragnosis generic technology development
○ Development of ligand labeling technology such as antibodies, peptides and aptamer on biodegradable particle
- Optimization of ligand and radioisotope labeling technology
- Confirm the tumor target imaging using ligand-biodegradable complex
○ In vitro evaluation of radio-labeling RGD conjugated nanoparticles uptake
- Development of three nanoparticle conjugates with RGD peptide ligands - Confirm the cell targeting concentration (IC50 < 5nM)
- In vitro stability test (>90%)
○ Development of ligand labeling technology using candidate nano-particle substances such as gold, oxidized iron, and polymers
- Confirm the targeted/non-targeted cell uptake ratio (>200%)
- Confirm imaging of cadidate nano-particle substances in vivo
○ Optimization of radio-isotope uptake in reporter gene trasfected stem/immune cells
- Confirm differentiation capacity of reporter gene introduced therapeutic stem cell
- Confirm the distribution of therapeutic stem cell in normal mouse

2. Optimization of radio-theragnosis generic technology development
○ Optimization of radio-labeling biodegradable particle for imaging and therapy of cancer
- Evaluation of in vitro uptake and in vivo imaging
- Mornitoring of therapeutic effect using theragnostic albumin
○ Optimization of radiolabeled nano theragnostic materials
- Development of therapeutic agent loaded liposome nanoparticle and chitosan hydrogel nanoparticle
- Therapeutic agent loaded double layered gold nanoparticle and HIFU treatment
- Development and evaluation of F-18 labeled RGD-SPION-drug
○ Optimization of cell tracking system using radiolabeled therapeutic stem / immune cells in in vivo model
- Establishment of cell labeling technique with the nuclear medicine probe
- Assessment of stability and safety of the nuclear medicine probe in in vitro
- Separation of microvesicles from tumor/immune cells and characterization of the microvesicles

3. Leading of clinical candidates in radio-theragnosis generic technology development
○ Leading of clinical candidates in radio-labeling biodegradable particle
- Optimization of targeted imaging and therapeutic effect using theragnostic albumin
- Evaluation of biodistribution using theragnostic albumin
○ Development of multi-modal imaging system using radiolabeled nanoparticles
- Evaluation of therapeutic agent loaded liposome nanoparticle and chitosan hydrogel nanoparticle
- Evaluation of correlation with imaging of F-18 labeled RGD-SPION-drug and angiogenesis
- Evaluation of therapeutic agent loaded double layered gold nanoparticle and HIFU treatment
○ Clinical applicable technology of radiolabeled therapeutic stem / immune cells
- Nuclear imaging of cell using nuclear medicine probe and combination with other imagings
- Optimization of nuclear molecular imaging and its applications
- Potentiation of therapetuic effect of cell therapy using microvesicle preapplication
○ Optimization of candidate material and GLP(good laboratory practice) test
- Optimization of conjugated number of ligands and linker on albumin surface
- Safety evaluation and toxicity test of nano probes

Expected Contribution
○ Radio-theragnosis medicine and technology development based on deduction of several nano-particle candidates, establishment of manufacturing technique and establishment of radio-labeling technology maximize the effect of research.
○ Theragnosis is a important technology for personalized therapy to monitoring drug and therapeutic materials, which makes imaging or radiotherapy possible simultaneously.
○ Theragnostic agents and theragnosis generic technology development will be helpful to reduction of psychological and economical difficulties and improvement of life quality of cancer patients.

( 출처 : SUMMARY 6p )

목차 Contents

• 표지 ... 1
• 제출문 ... 2
• 보고서 요약서 ... 3
• 요 약 문 ... 4
• SUMMARY ... 6
• C O N T E N T S ... 8
• 목차 ... 9
• 1. 연구개발과제의 개요 ... 10
• 2. 국내외 기술개발 현황 ... 15
• 3. 연구수행 내용 및 결과 ... 30
• 제1절 생분해입자를 이용한 방사선 테라그노시스 의약품 연구 ... 30
• 제2절 RGD 등 신생혈관추적 바이오마커 방사선표지 기술 개발 ... 60
• 제3절 골드/철/고분자나노입자를 이용한 방사선 테라그노시스 의약품 연구 ... 92
• 제4절 줄기/면역세포를 이용한 방사선 테라그노시스 의약품 연구 ... 244
• 4. 목표달성도 및 관련분야 기여도 ... 275
• 5. 연구결과의 활용계획 ... 281
• 제1절 경제적 측면 ... 281
• 제2절 사회적 측면 ... 281
• 제3절 기술적 측면 ... 282
• 제 4 절 추가연구의 필요성 ... 282
• 6. 연구과정에서 수집한 해외과학기술정보 ... 284
• 7. 연구개발결과의 보안등급 ... 287
• 8. 국가과학기술종합정보시스템에 등록한 연구시설·장비 현황 ... 288
• 9. 연구개발과제 수행에 따른 연구실 등의 안전조치 이행실적 ... 289
• 10. 연구개발과제의 대표적 연구실적 ... 290
• 11. 기타사항 ... 292
• 12. 참고문헌 ... 293
• 별첨 3 대표성과기술서 ... 295
• 별첨 4 연구성과실적서 ... 297
• 끝페이지 ... 342