초록

Ⅲ. 연구개발의 내용 및 범위
- pyridopyrazine 유도체의 기준물질의 합성
- 표지반응을 위한 pyridopyrazine 전구체 합성
- F-18 표지 pyridopyrazine 유도체 합성
- F-18표지 화합물을 이용한 생물학적 평가 (NSCLC cell과 normal cell의 섭취율을 비교)

Abstract ▼

Objectives: In recent years, pyridopyrazine derivatives have attracted much attention as Wnt/β-catenin signaling pathway inhibitors. Wnt/β-catenin signaling pathway was found to be overexpressed and implicated in a variety of human tumors, including colon cancers, lung cancers, leukemia. The aim of

Objectives: In recent years, pyridopyrazine derivatives have attracted much attention as Wnt/β-catenin signaling pathway inhibitors. Wnt/β-catenin signaling pathway was found to be overexpressed and implicated in a variety of human tumors, including colon cancers, lung cancers, leukemia. The aim of this study was to target Wnt/β-catenin signaling with pyridopyrazine derivatives labeled with [¹⁸F] will provide an effective approach for early imaging of cancers.
Methods: 2-(4-fluorobutoxy)-3-(phenylethynyl)pyrido[3,2-b]pyrazine was synthesized in six chemical steps from commercially available 2,3-diaminopyridine. 3-(phenylethynyl)-2-(4-tosyloxybutoxy)pyrido[3,2-b]pyrazine was radio-labeled with ¹⁸F-Kryptofix222-K₂CO₃ in CH3CN at 80 °C for 3 min to yield 2-(4-[¹⁸F]fluorobutoxy)-3-(phenylethynyl)pyrido[3,2-b]pyrazine.
Purification was done by semi-preparative reversed-phase HPLC. I n vitro studies were undertaken in H460 (large cell lung cancer cells), H1299 (non-small cell lung cancer cells), MCF10A (human breast epithelial cells).
2 x 10⁵ cells in 24-well plates were incubated in the presence of 20μCi of substrate for 30, 60, 20 min respectively. Following isolation of the cells, the amount of associated activity with the cells and medium was measured respectively. Data are expressed as normalized accumulation of probe in (dpm cells / dpm medium / μg total protein).
Results: 2-(4-fluorobutoxy)-3-(phenylethynyl)pyrido[3,2-b]pyrazine was obtained in 6% overall yield. 2-(4-[¹⁸F]fluorobutoxy)-3-(phenylethynyl)pyrido[3,2-b] pyrazine was prepared in 20% radiochemical yield (non-decay-correctedyield) with in 80 min including HPLC purification, evaporation of HPLC eluent.
The radiochemical purity exceeded 97%. Cell uptake studies revealed considerable differences In cell-associated activity between cancer cells and normal cells(MCF10A). There was ~2-fold higher accumulation in cancer cells compared to normalcells.
Conclusions: We have successfully synthesized F-18 labeled pyridopyrazine derivatives. The radiofluorated compound exhibited the expected cancer cell accumulation in vitro.

목차 Contents

• 표지 ... 1
• 제 출 문 ... 2
• 보고서 요약서 ... 3
• 요 약 문 ... 5
• SUMMARY ... 8
• CONTENTS ... 9
• 목 차 ... 10
• 제1장 연구개발과제의 개요 ... 11
• 1. 경제적 • 산업적 중요성 ... 11
• 2. 연구 개발의 필요성 ... 12
• 제2장 국내외 기술개발 현황 ... 14
• 1. 국외 연구개발 실적 ... 14
• 2. 국내 연구개발 실적 ... 15
• 3. 본 연구결과의 우수성 ... 15
• 제3장 연구개발수행 내용 및 결과 ... 16
• 1. pyridopyrazine 유도체의 기준물질 및 전구체의 합성 ... 16
• 2. F-18 표지 pyridopyrazine 유도체 합성 ... 20
• 3. F-18표지 화합물을 이용한 생물학적 평가 ... 21
• 제4장 목표달성도 및 관련분야에의 기여도 ... 24
• 1. 목표달성도 ... 24
• 2. 관련분야에의 기여도 ... 24
• 제5장 연구개발결과의 활용계획 ... 25
• 제6장 참고문헌 ... 26
• 연구성과(연구마루 입력성과) ... 27