• 산업공학
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• 제24권3호
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• pp.187-195
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• 2011

The automatic radiopharmaceutical module consists of several 2-way valves, couple of syringes, gas supply unit, heating(cooling) unit and sensors to control the chemical reagents as well as to help the chemical reaction. In order to control the actuators of radiopharmaceutical module, the process is tabulated using spread sheet as like excel. Unlike the common program, a trivial error is too critical to allowed in the process because the error can lead to leak the radioactive reagent and to cause the synthesis equipment failure during synthesizing. Hence, the synthesis process has been validated using graphic simulation while the operator checks the whole process visually and undergoes trial and error. The verification of the synthesis process takes a long time and has a difficulty in finding the error. This study presents a methodology to verify the process algebraically while the radiopharmaceutical module is converted to the network model. The proposed method is validated using actual synthesis process.

• 대한방사성의약품학회지
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• 제8권2호
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• pp.87-93
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• 2022

[¹⁸F]FDG is known as the most widely used radiopharmaceutical in the imaging field of nuclear medicine worldwide. With the introduction of PET equipment, the demand for [¹⁸F]FDG has increased and the production volume has also increased. However, in order to increase production, the use of ¹⁸F radioisotope must be increased or [¹⁸F]FDG must be synthesized in high yield. Therefore, in order to meet the high yield and purity of radiopharmaceuticals, a radiopharmaceutical automatic synthesizer was required. As the use of [¹⁸F]FDG increased, automated synthesizer manufacturers supplied various types of radiopharmaceutical automated synthesizers to the market. In this study, we developed a commercialized [¹⁸F]FDG radiopharmaceutical automatic synthesizer (sCUBE FDG) using a disposable cassette type that complies with GMP developed by FutureChem, a leading radiopharmaceutical company. We used sCUBE FDG to verify the production process, radiopharmaceutical's quality (radiochemical purity, etc.), and radiochemical yield of [¹⁸F]FDG. As a result of optimizing the automatic synthesis process and synthesizing a total of 30 times, the production time was 35 ± 3 minutes and the average production yield was 65.6%.

• 산업공학
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• 제24권2호
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• pp.156-163
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• 2011

The radiopharmaceutical synthesis for PET (positron emission tomography) is composed of chemical reactions using automated synthetical equipment. Due to the radioactive material, the automated equipment is being frequently developed to replace human operators who conduct dangerous, repetitive and dexterous operations. As to operation, the manipulating program is commonly coded using the spread sheet while the whole actuators are mapped in every step. The process map (program) is changed according to such parameters as temperature of reactor, keeping time, mixture sequence and amount of reagent. In cases of customizing the automated synthetical equipment or developing the new radiopharmaceuticals, lots of experiments should be conducted and the programming mistake is not allowed as it can lead abnormal control of the equipment to leak the radioactive materials. The exact process map has depended on trial and error manner. Thus, this study developed the methodology to tabulate the synthetical process to convert the process map automatically while the synthetical module formation is represented by a network model. The proposed method is validated using the actual radiopharmaceutical synthetical procedure.

• 전자공학회논문지
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• 제51권4호
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• pp.193-200
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• 2014

본 논문에서는 방사성 의약품의 자동합성장치에 사용되는 단채널 감마선 분광기를 보드 형태로 설계, 제작하고 그 특성을 측정 분석하였다. 감마선 검출을 위해 CZT (CdZnTe) spear 검출기를 이용하였고 아날로그 방식을 적용한 신호처리 보드의 형태로 감마선 분광기를 제작하였다. 측정을 위하여 방사성 물질인 Co-60을 시료로 사용하였으며, 최대 1173keV까지의 감마선 에너지 스펙트럼을 얻을 수 있었다. 아날로그 보드는 CZT spear 검출기에서 감마선을 검출하여 출력하는 신호를 적절히 변화시켜주기 위한 SF (shaping filter) 및 PHA (peak and hold amplifier)와 수치화된 감마선 신호 데이터를 계산하기 위한 ADC(analog to digital converter)와 FPGA (field programmable gate array)로 구성되었다.

• Nuclear Medicine and Molecular Imaging
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• 제43권5호
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• pp.478-486
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• 2009

목적: 화합물이 가지는 항바이러스 및 항암 작용으로 인하여 5-iododeoxyuridine 유도체들에 관한 연구는 매우 광범위하게 이루어져왔다. 방사 요오드가 치환된 이들 화합물에 대한 연구의 주요 목표는 체내 및 체외 평가 시 효과적 일뿐만 아니라, 보다 안정한 화합물을 개발하는 것이다. 본 연구를 통해, 다양한 방사성의약품의 중간체로도 이용되어질 수 있는 carbocyclic radioiododeoxyuridineanalogue (ddIVDU)를 합성하여 생물학적 평가를 수행하고자 하였다. 대상 및 방법: 목표 화합물의 합성은 Pd(0)-촉매 결합 반응, LAH 환원반응, hetero Diels-Alder 반응을 주요 반응으로 하여 수행하였다$(Sch\;3)^{10-12}$. 합성된 화합물의 생물학적 평가를 위해 MCA와 MCA-tk 세포에 다양한 농도의 GCV와 carbocyclic ddIVDV를 처리하여 MTS 법을 이용해 세포독성을 보았고, [$^{125}I$]carbocyclic ddIVDU를 이용해 MCA와 MCA-tk 세포에서 HSV1-tk에 의한 선택적 섭취를 비교 평가 하였다. 결과: Carbocyclic ddIVDU 및 요오드 도입을 위한 전구물질의 합성을 cyclopentadiene을 출발 물질로 하여 높은 수율에 의해 수행하였다. 방사요오드를 이용한 동위원소 도입 반응은 각각, 80% 이상의 방사표지 수율 및 95 % 이상의 방사 화학적 순도를 나타내었다. 세포독성 결과 MCA-tk 세포에서 carbodyclic ddIVDU는 GCV에 비해 세포독성이 작았고, MCA에서는 유사한 세포 독성을 보였다. [$^{125}I$]carbocyclic ddIVDU는 MCA-tk 세포에서 uptake는 8시간째까지 계속 증가하는 양상을 보였으며, MCA세포에서 uptake는 4시간째까지 일정하게 유지되다가 8시간째 급격히 증가하였다. [$^{125}I$]carbocyclic ddIVDU의 uptake는 MCA보다 MCA-tk에서 약 2-5배 정도 높은 결과를 보였다. 결론: 진행되어진 생물학적 결과로부터 이 유도체는 체내 평가 시 매우 안정할 뿐만 아니라, GCV에 비해 독성이 덜하고, HSV1-tk cell에 선택적임을 보여준다. 따라서 신규 화합물인 carbocyclic ddIVDU는 HSV1-tk를 영상화하는데 유용하게 이용되어질 수 있을 것이다.

• 방사선산업학회지
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• 제5권4호
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• pp.313-316
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• 2011

[$^{18}F$]FDG (2-[$^{18}F$] Fluoro-2-deoxy-D-Glucose), which is required Automated Synthetic Module for production, is most often used Radiopharmaceuticals in nuclear medicine. In this study, an Automated Synthesis Module was developed to produce FDG in two consecutive time when F-18 feds continuously by modifying a domestic FDG Automated Synthetic Module on structural geometry and control system. The results were showed that the Average Synthesis Yields on the developed Automated Synthetic Module were $45{\pm}3%$ (n=20), $50{\pm}3%$ (n=20) respectively. The Quality Control results, such as Radio TLC, Radiochemical purity, Gamma-counter, pH, LAL Test, Micro bacteria test, showed in same level with domestic [$^{18}F$]FDG Auto-Synthetic modules. Therefore, if some features were improved by considering the components life time and appearance, commercial sales can be expected because of low price and easy maintenance compared with foreign products.

• Bulletin of the Korean Chemical Society
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• 제32권6호
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• pp.1931-1935
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• 2011

The synthesis of carbocyclic analogues of normal nucleosides has grown exclusively since they have shown potential antiviral and antitumor activities. Radiolabeled cis-1-[4-(hydroxy-methyl)-cyclopent-2-enyl]-5-$[^{124}I]$-iodocytosine (carbocyclic d4IC) and cis-1-[4-(hydroxy-methyl)-cyclopent-2-enyl]-5-(2-$[^{124}I]$iodovinyl)cytosine(carbocyclic d4IVC) were synthesized. The synthetic route employed Pd(0)-catalyzed coupling reaction together with organotin and exchange reaction for radioiodination as key reactions. Carbocyclic $[^{124}I]$d4IC gave more than 75% radiochemical yield with greater than 95% radiochemical purity. Carbocyclic $[^{124}I]$d4IVC gave more than 80% radiochemical yield with greater than 95% radiochemical purity.

• Bulletin of the Korean Chemical Society
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• 제25권8호
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• pp.1147-1150
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• 2004

Hypericin (1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione), an antidepressant which is also known to be a potent protein kinase C (PKC) inhibitor was synthesized as a precursor for radioiodine labeling via two step reactions. Malignant glioma cells express higher PKC activity compared to untransformed glial cell. Here we report the synthesis and radioiodine labeling of hypericin as a potential brain tumor imaging radiopharmaceutical. The reference compound, 2-iodohypericin, and its radiolabelled analogues, 2-[$^{123}I$]iodohypericin and 2-[$^{124}I$]iodohypericin have been prepared by the reaction of hypericin with NaI or [$^{123}I$]NaI or [$^{124}I$]NaI. The labeling yield was 60-65% for each analogue and the optimal reaction time was 10 min. The purification and isolation of the labelled products were achieved by a reversed-phase HPLC.

• 방사선산업학회지
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• 제11권1호
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• pp.13-18
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• 2017

Recently, the number of PET cyclotrons has increased in Korea. A cyclotron mainly produces $^{18}F$, which is used for the production of [$^{18}F$]FDG, a cancer diagnostic radiopharmaceutical. For radiation protection, the discharge control standard under the Nuclear Safety Act limits the radioactive concentration of $^{18}F$ in the exhaust discharged from a nuclear power utilization facility to below $2,000Bq\;m^{-3}$. However, the radioactive concentration of $^{18}F$ discharged during [$^{18}F$]FDG production at the cyclotron facility at Chosun University is maintained at about $1,500Bq\;m^{-3}$ on average, which is 75% of the concentration limit of the discharge control standard, and temporarily exceeds the standard as per the real-time monitoring results. This study evaluated the performance of the exhaust filter unit of the cyclotron facility at Chosun University by assessing the concentration of $^{18}F$ in the exhaust, and an experiment was conducted on the discharge reduction, where $^{18}F$ is discharged without reacting with the FDG precursors during [$^{18}F$]FDG synthesis and is immediately captured by the [$^{18}F$]FDG automatic synthesis unit. Based on the performance evaluation results of the exhaust filter at the cyclotron facility of Chosun University, the measured capture efficiency before and after the filter was found to be 92%. Furthermore, the results of the discharge reduction experiment, where the exhaust $^{18}F$ was immediately captured by the [$^{18}F$]FDG synthesizer, showed a very satisfactory 94.3% reduction in the concentration of discharge compared to the existing discharge concentration.

• 방사선산업학회지
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• 제4권1호
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• pp.1-6
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• 2010

The purpose of this study is to synthesize the radio fluorine labelled isoquinoline salt derivative as new radiopharmaceutical for imaging tumors using positron emission tomography (PET). The planarity of isoquinoline allows to inhibit topoisomerase or intercalate between adjacent DNA base pairs, which result in producing double strand breaks in the DNA and a cell death. Therefore, the isoquinoline has seemed to have a potential anticancer activity. In order to obtain 2-(5-[$^{18}F$]fluoropentylisoquinolinium salt with good radiochemical yield, tosylated precursors have been synthesized. The labelling reaction was carried out for 30 minute in HMPA at $120^{\circ}C$. The radiochemical yield was about 50~60%.