보고서 정보
주관연구기관 |
한국원자력의학원 Korea Institute of Radiological & Medical Sciences |
보고서유형 | 최종보고서 |
발행국가 | 대한민국 |
언어 |
한국어
|
발행년월 | 2014-06 |
과제시작연도 |
2013 |
주관부처 |
미래창조과학부 Ministry of Science, ICT and Future Planning |
연구관리전문기관 |
한국연구재단 National Research Foundation of Korea |
등록번호 |
TRKO201400028401 |
과제고유번호 |
1345198646 |
사업명 |
방사선기술개발사업 |
DB 구축일자 |
2014-11-22
|
키워드 |
금속.방사성동위원소.방사성추적자.진단.PET.Metal.Radioisotope.Radiotracer.Diagnosis.
|
DOI |
https://doi.org/10.23000/TRKO201400028401 |
초록
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- 1단계 연구 수행을 통하여 Cu-64에 대한 생산 빈도 및 수율이 꾸준히 증가해오고 있으며, 현재 월 평균 3회 이상 생산이 이루어지고 있고, 매 생산시마다 100 mCi 이상의 수율을 보여주고 있으며, 특히 지난 2년 동안 생산성이 5배 이상 증가하였음.
- 2세부 과제의 비교평가용 연구 지원을 위한 I-124 연구의 경우 (p,2n) 핵반응에 의해 월 평균 2회 생산을 수행하고 있으며, 지난 2년 동안 생산성이 4배 이상 증가하였음.
- Y-86에 대한 생산은 Sr carbonate를 이용하여 디스크 타입으로 타겟
- 1단계 연구 수행을 통하여 Cu-64에 대한 생산 빈도 및 수율이 꾸준히 증가해오고 있으며, 현재 월 평균 3회 이상 생산이 이루어지고 있고, 매 생산시마다 100 mCi 이상의 수율을 보여주고 있으며, 특히 지난 2년 동안 생산성이 5배 이상 증가하였음.
- 2세부 과제의 비교평가용 연구 지원을 위한 I-124 연구의 경우 (p,2n) 핵반응에 의해 월 평균 2회 생산을 수행하고 있으며, 지난 2년 동안 생산성이 4배 이상 증가하였음.
- Y-86에 대한 생산은 Sr carbonate를 이용하여 디스크 타입으로 타겟을 만든 후, (p,n) 핵 반응을 통하여 실험을 수행하였으며, 국내 최초로 2013년에 Y-86에 대한 생산 기술력을 확보하였으며, 현재 시간당 약 4 mCi의 Y-86을 얻을 수 있는 단계에 있음.
- Zr-89의 생산은 natural yttrium foil을 이용하여 (p,n) 핵반응을 통해 실험을 수행하였으며, 국내 최초로 2012년도에 Zr-89에 대한 생산 기술력을 확보하였다. 고순도의 Zr-89를 얻을수 있도록 1회용 컬럼을 본 과제에서 자체 제작하였으며, 빔조사 및 회수 과정을 수행한 후, MCA 핵종 분석을 통하여 순수한 Zr-89가 얻어지는 것을 확인하였고. 현재 월평균 2회 생산을 수행하고 있으며, 시간당 7.5 mCi의 Zr-89를 얻을 수 있는 기술력을 확보하였음.
- 1세부 과제에서 생산되어진 동위원소는 2세부와 3세부 과제는 물론이고, 10여개 이상의 국내 관련 연구기관으로 연구 지원을 해옴으로써 국가의 연구 역량 강화에 기여하고 있음.
- 본 연구과제의 결과물들은 방사성의약품의 합성 및 자동화 기술을 향상시켜줄 것이며, 아울러 신규 핵종을 기반으로 하는 새로운 방사성의약품의 개발을 촉진하게 될 것으로 기대됨.
- Cu-64와 안정적으로 착물을 형성할 수 있는 거대고리 킬레이터 3종 (MM-TE2A, DM-TE2A, PCB-TE2A)을 개발하였으며 높은 수율로 Cu-64로 표지에 성공하였을 뿐만 아니라 실제로 체내에서 매우 우수한 안정도를 보임을 동물실험을 통해 검증하였음. 뿐만 아니라 항체를 효과적으로 표지할 수 있는 TE2A-NCS 이중기능킬레이트를 개발하여 핵의학영상을 통해 종양을 선택적으로 영상화할 수 있었음.
Abstract
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IV. Results of the Research
1. Building of stable support system for Cu-64 For production of Cu-64, we used (p,n) nuclear reaction and used duralumin and Ta foils as beam degraders in order to reduce beam energy. Because it is really difficult to control beam energy due to old cyclotron. Recently
IV. Results of the Research
1. Building of stable support system for Cu-64 For production of Cu-64, we used (p,n) nuclear reaction and used duralumin and Ta foils as beam degraders in order to reduce beam energy. Because it is really difficult to control beam energy due to old cyclotron. Recently, we produce Cu-64 more than three times in a month and have been supporting to domestic researchers. We obtained the production license in 2012 and this document give us the information for radiochemical quality. We made the standardization of production and designed the separation equipment by semi automation, so the method of production and its application were successfully stablished. Production has increased steadily and we produced three times in a month and obtained more than 100 mCi, each time. The productivity five-fold in just two years. And till April 2014, we have already supported Cu-64 more than 8,200 mCi to domestic researchers. So we have contributed to the strengthening national research and more than 3,800 million won are earned for importing effect. Recently, the study for building more efficient production system is performed by using new target device. New target device is the specialized target system for our MC-50 cyclotron. It was designed to proceed nuclear reaction more efficiently and to maximize the cooling effect during the beam irradiation. The successful development of Cu-based radiopharmaceuticals is highly dependent on the proper choice of bifunctional chelator as well as targeting biomolecules. We synthesized TE2A in efficient way, and found that TE2A makes much more stable Cu complex compare with DOTA and TETA.
Furthermore, we developed TE2A analogue, TE2A-benzyl-NCS, which can easily conjugate with antibody. We also developed propylene-cross-bridged TE2A (PCB-TE2A), which makes ultrastable Cu(II) complexes. 64Cu-PCB-TE2A showed higher in vitro and vivo stability than ethylene-cross-bridged TE2A (ECB-TE2A).
And we designed and synthesized DM-TE2A as a structural analogue of ECB-TE2A. DM-TE2A also showed excellent kinetic stability even though cross-bridge was broken.
2. Study of production and collection technology for Y-86
In 2013, we had secured the production technology of Y-86 for the first time in Korea. For production of Y-86, we used (p,n) nuclear reaction by using Sr carbonate and production was carried out research as a way of making powder based on disc type target. And currently, we can get the Y-86 by 4 mCi per hour. In the near future, we have plan to produce Y-86 according to research schedule and will support to domestic researchers.
3. Building of stable support system for I-124
For production of I-124, we used (p,2n) nuclear reaction by using 125TeO2. Recently, we produce twice a month and have been supporting to domestic researchers. The production and supply have increased steadily each year and we are gradually observing improvement in our quality. Especially, the productivity four-fold in just two year. And till April 2014, we have already supported I-124 more than 1,600 mCi to domestic researchers. So we have contributed to the strengthening national research and more than 690 million won are earned for importing effect.
4. Study of production and collection technology for Zr-89
Zr-89 has long physical half-life and this allow the use of Zr-89 in PET applications with monoclonal antibodies, which posses long biological half-lives up to several days. We developed production technology of Zr-89 in 2012. For production of Zr-89, we used (p,n) nuclear reaction by using natural yttrium foil. The productivity increased 37 times compared to the previous year. And currently, we can get the Zr-89 by 7.5 mCi per hour.
We designed and manufactured disposable column for purification, and developed the high purity refining process. After beam irradiation, we confirmed Zr-89 was obtained purely from the MCA analysis.
We have carried out experiment by the synthesis of Zr-herceptin, and from the result, Zr-89 from the KIRAMS formed stable complexes with antibody and was confirmed the possibility as diagnostic radiopharmaceuticals. Shortly, we have plan to produce Zr-89 according to research schedule and will support to domestic researchers.
5. Development of chelators forming ultra stable Cu complexes
Even though Cu-64 shows attractive decay mode (both beta+ and beta-), current widely used chelators such as DOTA and TETA loose free Cu(II) ions in vivo due to non-optimized stability of their Cu complexes. Therefore, new helators showing high in vivo stability are highly needed. During last three years, new three chelators (MM-TE2A, DM-TE2A, PCB-TE2A) were developed. Three chelators were radiolabeled in quantitative radiolabeling yield using optimized labeling conditions. Furthermore, the radiolabeled chelators showed ultra high in vivo stability in animal model experiments. New bifunctional chelator based on TE2A was developed. It showed excellent conjugation ability with antibody and its 64Cu-labeled antibody conjugate detected tumor clearly in tumor animal models.
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