• Nuclear Medicine and Molecular Imaging
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• 제40권5호
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• pp.263-270
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• 2006

목적: 종양 내 양전자방출단층촬영으로 세포증식을 영상화하기 위해 $[^{11}C]$thymidine과 같은 다양한 방사성의약품이 개발되었다. 그러나 $[^{11}C]$thymidine은 C-11의 짧은 반감기와 대사과정의 추적에 문제점을 가지고 있어 문제점을 해결하기 위해 $[^{11}C]$thymidine을 대신하여 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT)이 개발이 보고되었다. 본 연구에서는 thymidine을 출발물질로 하여 총 6 단계에 걸쳐 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT)의 합성 하였다. 또한 합성된 $[^{18}F]$FLT를 이용하여 FET, FDG의 9L 세포에서 세포섭취율을 비교하였으며 생체 분포 및 양전자방출단층촬영 영상을 얻어 유용성을 검증하고자 하였다. 대상 및 방법: $[^{18}F]$FLT 전구체 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimet hoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-${\beta}$-D-threopentofuranosyl)thymine는 N3-위치에 tert-butoxycarbony (t-Boc)기를 도입하고, 3'-위치에 친핵성 치환반응을 유도하기 위한 이탈기로 nitrobenzenesulfonyl기를 도입하였다. 방사성동위원소 $^{18}F$의 표지는 전구체를 $120^{\circ}C$, acetonitrile 용매하에서 수행하였고 0.5 N HCl로 보호기를 제거하였다. 표지된 $[^{18}F]$FLT를 alumina N step-pak과 고성능액체크로마토그래피를 이용하여 정제하였다. $[^{18}F]$FLT의 세포섭취율은 $[^{18}F]FET,\;[^{18}F]FDG$와 9L 세포에서 비교하였고, 체내동태는 종양세포를 이식한 쥐를 이용하여 10분, 30분, 60분, 120분에 측정하였으며, 양전자방출단층촬영 영상을 얻었다. 결과: HPLC 분리 후 $[^{18}F]$FLT의 방사화학적 수율은 약 20-30% 정도였고 방사화학적 순도는 95% 이상이었다. 시험관 섭취율에서 $[^{18}F]$FLT는 시간이 지남에 따라 증가하는 양상을 보였고 생체분포 실험에서 주사 후 120분에서 tumor/blood, tumor/muscle, tumor/brain의 비율은 $1.61{\pm}0.34,\;1.70{pm}0.30,\;9.33{\pm}2.22$를 나타내었다. 또한, 양전자방출단층촬영 결과 종양에 국소화된 영상을 얻었다. 결론: $[^{18}F]$FLT의 종양세포 섭취는 정상 뇌에 비해 월등히 높게 나타났으며, 양전자방출단층 촬영 결과는 뇌종양 진단을 위한 방사성의약품으로 유용하게 이용될 수 있을 것으로 기대된다.

• Bulletin of the Korean Chemical Society
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• 제32권7호
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• pp.2410-2412
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• 2011

Using a single step chemical synthesis, we synthesized the potential tumor imaging agent $^{99m}Tc$-diglucose-diethylenetriamine (DGTA) from diethylenetriamine and natural D-glucose. 10 min Incubation of 10 mg of precursor with 50 ${\mu}g$ of $SnCl_2{\cdot}2H_2O$ at room temperature yielded over 95% of $^{99m}Tc$ labeling. The stability for 6 hours in saline or human plasma was over 90%. In vitro tumor cell uptake assays using the SNU-C5 and 9 L cell lines showed that, in 0-400 mg/dL glucose medium, cell uptake of $^{99m}Tc$-DGTA was 1.5-8 times higher than that of [$^{18}F$]FDG. Moreover, [$^{18}F$]FDG uptake was dependent on glucose concentration in the medium, whereas cellular uptake of $^{99m}Tc$-DGTA was not dependent on glucose concentration, suggesting that the two compounds have different uptake mechanisms by tumor cells.

• 대한핵의학회지
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• 제38권2호
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• pp.198-204
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• 2004

Tumor cell proliferation is considered to be a useful prognostic indicator of tumor aggressiveness and tumor response to therapy but in vitro measurement of individual proliferation is complex and tedious work. PET imaging provides a noninvasive approach to measure tumor growth rate in situ. Early approaches have used $^{18}F$-FDG or methionine to monitor proliferation status. These 2 tracers detect changes in glucose and amino acid metabolism, respectively, and therefore provide only an indirect measure of proliferation status. More recent studies have focused on DNA synthesis itself as a marker of cell proliferation. Cell lines and tissues with a high proliferation rate require high rates of DNA synthesis. $[^{11}C]Thymidine$ was the first radiotracer for noninvasive imaging of tumor proliferation. The short half-life of $^{11}C$ and rapid metabolism of $[^{11}C]Thymidine$ in vivo make the radiotracer less suitable for routing use. Halogenated thymidine analogs such as 5-iodo-2-deoxyuridine (IUdR) can be successfully used as cell proliferation markers for in vitro studies because these compounds are rapidly incorporated into newly synthesized DNA. IUdR has been evaluated as a potential in vivo tracer in nuclear medicing but the image qualify and the calculation of proliferation rates are impaired by its rapid in vivo degradation. Hence, the thymidine analog $3'-deoxy-3'-^{18}F-fluorothymidine$ (FLT) was recently introduced as a stable proliferation marker with a suitable nuclide half-life and stable in vivo. $[^{18}F]FLT$ is phosphorylated to 3-fluorothymidine monophosphate by thymidine kinase 1 and reflects thymidine kinase 1 activity in proliferating cell. $[^{18}F]FLT$ PET is feasible in clincal use and well correlates with cellular proliferation. Choline is a precursor for the biosynthesis of phospholipids (in particular, phosphatidylcholine), which is the essential component of all eukaryotic cell membranes and $[^{11}C]choline$, which is a new marker for cellular proliferation.

• Nuclear Medicine and Molecular Imaging
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• 제43권2호
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• pp.91-99
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• 2009

Noninvasive imaging of molecular and biological processes in living subjects with positron emission tomography(PET) provides exciting opportunities to monitor metabolism and detect diseases in humans. Measuring these processes with PET requires the preparation of specific molecular imaging probes labeled with $^{18}F$-fluorine. In this review we describe recent methods and novel trends for the introduction of $^{18}F$-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic $^{18}F$-fluorination of some halo- and mesyloxyalkanes to the corresponding $^{18}F$-fluoroalkanes with $^{18}F$-fluoride obtained from an $^{18}O(p,n)^{18}F$ reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for $^{18}F$-fluorine labeling. Ionic liquid method is rapid and particularly convenient because $^{18}F$-fluoride in $H_2O$ can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. The nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with $^{18}F$-fluorine for PETimaging, and it is illustrated by the synthesis of $^{18}F$-fluoride radiolabeled molecular imaging probes, such as $^{18}F$-FDG, $^{18}F$-FLT, $^{18}F$-FP-CIT, and $^{18}F$-FMISO, in high yield and purity and in shorter times compared to conventional syntheses.

• 대한핵의학회지
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• 제35권3호
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• pp.117-124
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• 2001

Serum thyroglobulin measurement and I-131 whole-body scintigraphy (WBS) are well-established methods for the detection of recurrence in the follow-up of patients with thyroid carcinoma. However, inconsistent results are observed frequently, and these two methods are not always able to detect recurrence. In some patients, serum thyroglobulin level is elevated but the WBS is negative, because the recurrent tumor is too small and below the sensitivity of the diagnostic scan, or there is a dissociation between thyroglobulin synthesis and the iodine frapping mechanism. In such cases, various nuclear imaging methods including Tl-201 Tc-99m-sestamibi, and F-18-FDG PET can be used besides anatomical imaging methods. Among them, FDG PET localizes recurrent lesions in WBS-negative thyroid carcinoma with high accuracy. Several studies have suggested that empirical high-dose I-131 therapy resulted in a high rate of visualization in post-therapy scans with evidence of subsequent improvement. An important question is when to operate on patients with recurrent tumor. We believe that surgical removal is the best means of treatment for patients with localized persistent tumor, despite the high-dose I-131 therapy. with tumor in thyroid remnant, and with isolated recurrence in the lymph node, lung or bone. In addition, we recommend palliative resection of locally unresectable mass with subsequent treatment with high-dose I-131 therapy. Before I-131 therapy, the evaluation of sodium-iodide symporter expression in thyroid carcinoma can predict iodine uptake. Retinoic acid is known to induce redifferentiation, and to enhance I-131 uptake in thyroid carcinoma. Retinoic acid therapy may represent an alternative approach before high-dose I-131 therapy.

• 핵의학기술
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• 제12권1호
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• pp.74-77
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• 2008

The radiopharmaceuticals are routinely injected to blood vessel for acquiring PET image. For this reason, It is imperative that they undergo strict quality control measures. Especially, Sterility test is more important than any other quality control procedures. According to the FDA guideline, It requires filter integrity test used in the processing of sterile solutions. Among several methods, we can decide to use bubble point test. We usually use vented GS-filters (Millipore co., USA) which are sterilizinggrade (0.22 um pore size) and are placed upper site on product vial. After the synthesis of $^{18}F$-FDG, solutions wet the membrane in filter and then go into the product vial. By all synthesis steps have finished, we can observe the presence of the bubbles in the product vial. Since we have started this study, we have never found any bubbles in the product vial. Because the maximum pressure intensity of the filter which has set by manufacturer is up to 5 bars, but helium gas pressure is up to 1 bar in our module system. So, we can make 5 bars pressure using helium gas bombe and increase pressure up to 5 bars step by step. However, it does not happen to anything in vial.

• 방사선산업학회지
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• 제11권1호
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• pp.39-45
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• 2017

A cyclotron is a kind of particle accelerator that produces a beam of charged particles for the production of medical, industrial, and research radioisotopes. More than 30 cyclotrons are operated in Korea to produce $^{18}F$, an FDG synthesis at hospitals. A 30-MeV cyclotron was installed at ARTI (Advanced Radiation Technology Institute, KAERI) mainly for research regarding isotope production. In this study, we analyze and estimate the items of risk such as the problems in the main components of the cyclotron, the loss of radioactive materials, the leakage of coolant, and the malfunction of utilities, fires and earthquakes. To estimate the occurrence frequency in an accident risk assessment, five levels, i.e., Almost certain, Likely, Possible, Unlikely, and Rare, are applied. The accident consequence level is classified under four grades based on the annual permissible dose for radiation workers and the public in the nuclear safety law. The analysis of the accident effect is focused on the radioactive contamination caused by radioisotope leakage and radioactive material leakage of a ventilation filter due to a fire. To analyze the risks, Occupation Safety and Health Acts is applied. In addition, action plans against an accident were prepared after a deep discussion among relevant researchers. In this acts, we will search for hazard and introduce the risk assessment for the research 30-MeV cyclotron facilities of ARTI.

• 핵의학기술
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• 제16권2호
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• pp.126-130
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• 2012

방사성의약품 제조 시 휘발성 기체의 경우에 완전 차폐가 되지 않고, Hot cell 외부로 그리고 배기덕트를 통해 작업자에게 외부피폭은 물론 호흡을 통해 내부피폭을 가져오게 한다. 처음에는 Hot cell 자체의 배출구를 막아서 방사성기체를 차단하려하였으나 장치에 맞는 기체 밀폐형 댐퍼의 제작이 어렵고, 크기가 맞지 않아서 설치 후에 여전히 문제점이 개선되지 않았다. 그러나 Tedlar gas sampling bag의 사용으로 합성 장치의 가스 배출구를 연결하여 방사성 기체를 저장하고 10반감기가 지난 후에 배출함으로써 작업자의 피폭을 확연히 줄이게 되었으며 $^{18}F$ 방사성 기체는 Hot cell 배출구에 활성탄 필터를 연결하고 최종 배출구에 2차 활성탄 필터를 사용함으로써 배출되는 방사능 농도를 90% 이상 줄여주었다. 단 반감기의 핵종인 경우는 위와 같은 경우를 이용하여 다음날 작업을 할 수 있지만 반감기가 긴 핵종들 같은 경우는 다음날 처리 할 수 없는 문제점들이 발생한다. Decay tank의 추가적인 문제점들을 보완하거나 기체상의 여러 방사성 입자들을 포집 할 수 있는 물질들이 만들어져야 할 것이다. 현재 우리나라는 최종 배출 공기 중 방사능 농도만을 규제하고 있으나 유럽 같은 경우 일일 배출 양과 연간 배출도 규제를 하고 있다. 방사성의약품 합성 시 발생하는 많은 방사성 물질들을 보다 효과적으로 친환경적으로 처리할 수 있는 여러 연구들이 이루어져야 할 것이다.

• 대한방사선기술학회지:방사선기술과학
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• 제35권2호
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• pp.141-149
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• 2012

최근 최첨단 핵의학 영상기술의 발달로 임상적 이용이 증가되어 방사선 선원을 취급하는 핵의학과 작업종사자의 몸통 부위와 손 부위에 노출되는 외부 피폭선량을 평가하고 검사 빈도가 높은 전신 뼈검사(Whole body Bone Scan)와 양전자 단층촬영(PET/CT)시 방사선 선원($^{99m}Tc$-HDP, $^{18}F$-FDG)의 취급 및 검사에 따른 손 부위 피폭선량을 측정하고자 한다. 방사선 선원 취급 시 방호구 착용 및 손 부위를 측정 할 수 있는 선량계 보유 여부를 알아보기 위해 4개의 의료기관에 설문 하였다. 방사선 선원을 직접 분주하고 주사하는 숙련된 작업종사자의 가슴과 약지손가락에 열형광 선량계을 착용하여 누적된 외부 방사선 선량을 측정하고 손 부위의 외부 방사선량 측정을 위해 구간별 일일 방사선 선원으로부터 노출되는 선량과 시간을 포켓도시메터를 이용하여 각각 측정 하였다. 인천광역시 4개 의료기관을 대상으로 조사한 결과 손 부위의 방사선 피폭선량 측정기를 구비한 의료기관은 1곳을 제외한 3곳은 구비하지 않았고 차폐기구 사용은 방사선 선원으로부터 몸통을 보호하기 위해 차폐기구를 사용한 곳이 대부분 이었고, 일부 의료기관에서는 사용하지 않는 곳도 있었다. 방사선 선원을 직접 분배하고 투여하는 핵의학과 작업종사자의 손 부위 외부피폭 선량은 몸통부위보다 약 2배 이상 많은 선량을 받았고, 검사 빈도가 높은 전신 뼈 검사와 양전자 단층촬영 시 각 구간별 외부피폭 선량을 보면 방사성의약품 합성 및 분배용기 장착, 분배, 투여, 이동 순으로 각각 나타났다. 또한 방사선 선원 투여시 방호구 착용 전/후 손 부위의 피폭선량을 측정한 결과 통계적 유의한 차이가 있었다. 연구결과 작업종사자의 유효선량에는 못 미치지만 비 작업종사자보다 비교적 높은 선량을 받고 있어 방사선 선원을 근거리에서 노출되는 작업종사자는 안전관리 규정을 준수하고 손 부위 선량계(Ring TLD)를 착용하여 방사선 선원으로부터 피폭 저감을 위한 활동을 하여야 한다.