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자동합성장치를 이용한 [$^{18}F$]Fallypride의 합성
박준형,문병석,이홍진,이효준,이인원,이병철,김상은,Park, Jun-Hyung,Moon, Byung-Seok,Lee, Hong-Jin,Lee, Hyo-Jun,Lee, In-Won,Lee, Byung-Chul,Kim, Sang-Eun 대한핵의학기술학회 2010 핵의학 기술 Vol.14 No.2
$[^{18}F]$Fallypride는 뇌의 도파민(dopamine) $D_2/D_3$ 수용체 (receptor)에 특이적으로 결합하는 길항제(antagonist)로 대뇌피질의 도파민 기능을 규명하기 위하여 많이 사용되어지는 방사성의약품이다. 그동안 발표되어진 자동 합성화 장치를 이용한 [$^{18}F$]Fallypride 합성은 20~30%의 낮은 합성 수율과 33~63 GBq/mmol의 낮은 비방사능이 보고되어졌고, 또, 상대적으로 긴 표지시간과 높은 농도의 base를 사용하기 때문에 다양한 부산물이 생성되어 정제의 어려움이 있어 임상에 사용되기에 한계가 많았었다. 본 연구에서는 다목적 F-18 합성장치인 GE TracerLab $FX_{FN}$ 모듈을 사용하여 base 농도를 최소화할 수 있는 연구를 수행하였고, [$^{18}F$]fallypride 합성에 적용하여 높은 합성수율과 비방사능(specific activity) 및 방사화학적 순도(radiochemical purity)를 합성하는 최적의 조건을 찾을 수 있었다. 이를 바탕으로 $66{\pm}1.4%$ (decay-corrected, n=28)의 높은 합성수율과 HPLC 분리, SPE 정제시간을 포함하여 총 $51{\pm}1.2$분에 빠르게 합성할 수 있었다. 합성 후, 품질관리 테스를 해 본 결과, 방사 화학적 순도는 95%이상, 비방사능은 166~470 $GBq/{\mu}mol$이었다. 본 연구에서 사용된 합성법은 [$^{18}F$]Fallypride를 이용한 dopamine $D_2/D_3$ 연구의 임상적 사용에 도움이 될 것이며, 낮은 농도의 base를 사용한 이 F-18 추출방법은 base에 민감한 전구체의 자동합성 생산에 유용할 것으로 사료된다. Purpose: $[^{18}F]$Fallypride plays an effective radiotracer for the study of dopamine $D_2/D_3$ receptor occupancy, neuropsychiatric disorders and aging in humans. This tracer has the potential for clinical use, but automated labeling efficiency showed low radiochemical yields about 5~20% with relatively long labelling time of fluorine-18. In present study, we describe an improved automatic synthesis of [$^{18}F$]Fallypride using different base concentration for routine clinical use. Materials and Methods: Fully automated synthetic process of [$^{18}F$]Fallypride was perform using the TracerLab $FX_{FN}$ synthesizer under various labeling conditions and tosyl-fallypride was used as a precursor. [$^{18}F$]Fluoride was extracted with various concentration of $K_{2.2.2.}/K_2CO_3$ from $^{18}O$-enriched water trapped on the ion exchange cartridge. After azeotropic drying, the labeling reaction proceeded in $CH_3CN$ at $100^{\circ}C$ for 10 or 30 min. The reaction mixture was purified by reverse phase HPLC and collected organic solution was exchanged by tc-18 Sep-Pak for the clinically available solution. Results: The optimal labeling condition of [$^{18}F$]Fallypride in the automatic production was that 2 mg of tosyl-fallypride in acetonitrile (1 mL) was incubated at $100^{\circ}C$ for 10 min with $K_{2.2.2.}/K_2CO_3$ (11/0.8 mg). [$^{18}F$]Fallypride was obtained with high radiochemical yield about $66{\pm}1.4%$ (decay-corrected, n=28) within $51{\pm}1.2$ min including HPLC purification and solid-phase purification for the final formulation. Conclusion: [$^{18}F$]Fallypride was prepared with a significantly improved radiochemical yield with high specific activity and shorten synthetic time. In addition, this automated procedure provides the high reproducibility with no synthesis failures (n=28).
한국형 사이클로트론(KOTRON-13)을 이용한 $[^{11}C]CO_2$ 생산과 다양한 $^{11}C$-표지 방사성의약품 생산 적용
이홍진,박준형,문병석,이인원,이병철,김상은,Lee, Hong Jin,Park, Jun Hyung,Moon, Byung Seok,Lee, In Won,Lee, Byung Chul,Kim, Sang Eun 대한핵의학기술학회 2012 핵의학 기술 Vol.16 No.2
최근 늘어나는 [$^{18}F$]FDG-PET 검사 증대와 더불어 새로운 방사성의약품으로 [$^{11}C$]아세테이트 검사가 신설되고 다양한 연구용 $^{11}C$-표지 방사성의약품 이용이 증대되고 있다. 본 연구에서는 성공리에 수행한 한국형 사이클로트론의 $^{11}C$-표적시스템을 이용하여, $[^{11}C]CO_2$ 생산 최적화 및 임상에서 사용가능한 $^{11}C$-표지 방사성의약품 생산 적용 연구를 수행하였다. Purpose : The KOTRON-13 cyclotron was developed and installed in regional cyclotron centers to produce short-lifetime medical radioisotopes. However, this cyclotron has limited capacity to produce $^{11}C$ so far. In present study, we developed an effective $^{11}C$ target system combining with fluorine-18 target and applied to the production of various $^{11}C$ radiopharmaceuticals. Materials and Methods : To develop the optimal $^{11}C$ target system and effective its cooling system, we designed the $^{11}C$ target system by Stopping and Range of Ions in Matter (SRIM) simulation program and considered the cavity pressure during irradiation at target grid. In this investigation, we modified target materials, cavity shapes and the position of cooling system in $^{11}C$ target and then evaluated $[^{11}C]CO_2$ production at different beam currents, thickness of the target foil, oxygen content of nitrogen gas and target gas loading pressure. Also, we evaluate the production of several $^{11}C$ radiopharmaceuticals such as [$^{11}C$]PIB, [$^{11}C$]DASB, and [$^{11}C$]Clozapine. Results : $[^{11}C]CO_2$ was produced about 74 GBq for 30min irradiation at 60 ${\mu}A$ of beam current as following conditions: thickness of the target foil: 19 nm HAVAR, oxygen content of nitrogen: under 50 ppb, target gas loading pressure: 24 bar. Additionally, the cooling system was stable to produce $[^{11}C]CO_2$ at high beam current. The radiochemical yields of [$^{11}C$]PIB, [$^{11}C$]DASB, and [$^{11}C$]Clozapine showed about 26-38% with over 127 GBq/umol of specific activity. Conclusion : The carbon-11 target system in the KOTRON-13 cyclotron was successfully developed and showed stable production of $[^{11}C]CO_2$. These results showed that our $^{11}C$ target system will be compatible with other commercial system for the routine $^{11}C$ radiopharmaceuticals production in the KOTRON-13 cyclotron.
3′-[(18)F]Fluoro-3′-deoxythymidine의 합성과 9L glioma 세포를 이식한 래트에서의 체내동태에 관한 연구
심아영 ( Ah Young Shim ),문병석 ( Byung Seok Moon ),이태섭 ( Tae Sup Lee ),이교철 ( Kyo Chul Lee ),안광일 ( Gwang II An ),양승대 ( Seung Dae Yang ),유국현 ( Kook Hyun Yu ),천기정 ( Gi Jeong Cheon ),최창운 ( Chang Woon Choi ),임상 대한핵의학회 2006 핵의학 분자영상 Vol.40 No.5
KOTRON-13 사이클로트론의 고효율C-11 가스 표적장치
이홍진,이원경,박준형,문병석,이인원,채성기,이병철,김상은,Lee, Hong-Jin,Lee, Won-Kyeong,Park, Jun-Hyung,Moon, Byung-Seok,Lee, In-Won,Chae, Sung-Ki,Lee, Byung-Chul,Kim, Sang-Eun 대한핵의학기술학회 2011 핵의학 기술 Vol.15 No.1
최근 들어 양전자방출단층촬영(positron emission tomography, PET) 대표적인 진단검사인 FDG (2-[$^{18}F$]fluoro-2-deoxy-D-glucose)를 이용한 전신암 및 장기별 대사 검사뿐만 아니라 또 다른 양전자 방출 동위원소 탄소-11로 표지 된 다양한 방사성의약품 사용이 증가될 예정이다. 본 논문에서는 현재 국내에 설치 보급되어있는 국산 KOTRON-13 사이클로트론에 냉각 성능이 개선된 탄소-11 표적 장치를 설계, 제작하고, 다양한 생산시험을 통하여 탄소-11의 생산량 증대를 입증 하였다. 성공적으로 기존의 불소-18 타겟과 새로운 탄소-11 타겟 호환장치를 도입하였고, 실험 결과 고효율 탄소-11표적 장치가 내수성이 우수하고, 30분 조사 시 최대 2,000 mCi를 생산하였다. 본 시험결과를 통해 향후 불소-18만이 생산 가능했던 국산 KOTRON-13 사이클로트론에 효율적이고 안정적으로 탄소-11생산 시스템을 도입할 수 있음을 증빙하였다. Purpose: The KOTRON-13 cyclotron was developed in South Korea and was introduced to regional cyclotron centers to produce short-lifetime medical radioisotopes. However, this cyclotron has limited capacity to produce carbon-11 isotope so far. We herein study how to develop and optimize an effective carbon-11 target system in the KOTRON-13 cyclotron by changing cooling system, combing with fluorine-18 target and evaluating beam currents. Materials and Method: To develop the optimal carbon-11 target and an effective cooling system, we designed the carbon-11 target system by Stopping and Range of Ions in Matter (SRIM) simulation program and considered the cavity pressure during irradiation at target grid. In this investigation, we evaluated the yield of carbon-11 production at different beam currents and the stability of the operation of the KOTRON-13 cyclotron. Results: The production of carbon-11 was enhanced from about 1.700 mCi ($50{\mu}A$) to 2,000 mCi ($60{\mu}A$) on the carbon-11 target which developed by seoul national university bundang hospital (SNUBH) and Samyoung Unitech. Additionally, the cooling condition was showed stable to produce carbon-11 under high beam current. Conclude: The carbon-11 target system of the KOTRON-13 cyclotron was successfully developed and improved carbon-11 production. Consequently, the operation of carbon-11 target system was highly effective and stable compare with other commercial cyclotrons. Our results are believed that this optimal carbon-11 target system will be helpful for the routine carbon-11 production in the KOTRON-13 cyclotron.
朴成天,文炳錫 東新大學校 工業技術硏究所 1999 工業技術硏究 Vol.5 No.-
The applicability of the system theoretic artificial neural network approach in developing effective nonlinear models of the rainfall-runoff process is demonstrated in this paper. The multi-layer networks, specially three-layer artificial neural networks have been used to model the rainfall-runoff process. And the data from the river Young-San has been utilized for the present study. This paper presents the potential of artificial neural network for simulating the hydrologic behavior of watersheds. The results of this paper suggest that the artificial neural network approach may provide a superior alternative to other methods of modeling for developing input-output simulation and forecasting models in situations that do not require modeling of the internal structure of the watershed.