• Nuclear Medicine and Molecular Imaging
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• 제40권4호
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• pp.228-232
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• 2006

목적 : $[^{18}F]F_2\;(T_{1/2}=110\;min)$ 기체를 이용하여 친전자성 치환반응으로 방사성동위원소 $^{18}F$을 표지하는 방법은 새로운 앙전자방출단층촬영용 방사성의약품 개발 분야에서 유용하게 이용되고 있다. 그림에도 불구하고 $[^{18}F]F_2$를 높은 생산수율과 비방사능으로 생산하기 위한 표적 개발 연구는 아직도 진행 중에 있다. 본 연구에서는 친핵성 치환반응으로 $^{18}F$을 도입하기 어려운 방사성의약품에 친전자성 치환반응으로 방사성동위원소를 도입할 수 있는 $[^{18}F]F_2$ 가스의 효율적인 생산에 관해 연구하였다. 대상 및 방법: 표적은 원추형 모양의 알루미늄 재질로 제작하였다. $[^{18}F]F_2$ 생산을 위한 핵반응으로 $^{18}O(p,n)^{18}F$를 사용하였으며, two-step 빔 조사방법을 이용하였다. 첫 번째 조사는 농축 $[^{18}O]O_2$가스를 표적에 충진한 후 빔 조사하여 $^{18}O(p,n)^{18}F$ 핵반응을 일으킴으로써 $^{18}F$를 생산한다. 생산된 $^{18}F$은 표적 챔버 기벽에 흡착된다. $[^{18}O]O_2$은 재사용을 위하여 냉각포획법으로 회수하였으며, $^{18}F$를 회수하기 위해 $[^{19}F]F_2/Ar$ 가스를 충진한 후, 두 번째 빔을 조사하여 방사성불소를 회수하는 방법으로 구성된다. 본 연구에서는 최적의 방사성불소 생산 조건을 찾기 위해 빔 조사 시간, 빔 전류 세기 농축 $[^{18}O]O_2$ 충진 압력 등의 변화에 따라 생산량을 평가하였다. 결과: 빔 조사 시간, 빔 전류, 농축 $[^{18}O]O_2$ 충진 압력 등의 조건을 변화시키면서 생산량을 평가한 결과 최적의 빔 조사 조건은 다음과 같다. 첫 번째 조사: 농축 $[^{18}O]O_2$을 약 15.0 bar충진, 13.2 MeV, 30 ${\mu}A$로 60-90분 조사; 두 번째 조사: 1% $[^{19}F]F_2/Ar$혼합가스 12.0 bar 충진, 13.2 MeV, 30 ${\mu}A$로 20-30분 조사 후 아르곤 가스로 회수하였을 때 EOB(end of bombardment) 기준으로 약 $34{\pm}6.0$ GBq(n>10)의 $[^{18}F]F_2$를 얻었다. 결론: $^{18}O(p,n)^{18}F$ 핵반응을 이용하여 친전자성 방사성동위원소 $[^{18}F]F_2$를 생산하였다. 표적 챔버는 알루미늄으로 제작하였으며 본 연구에서 연구된 $[^{18}F]F_2$가스는 친핵성 치환반응으로 방사성동위원소를 도입하기 어려운 다양한 방사성의 약품개발에 유용하게 이용될 수 있을 것이다.

• 핵의학기술
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• 제20권2호
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• pp.42-45
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• 2016

$^{18}F-Florbetaben$은 베타아밀로이드 병리를 확인하여 인지 장애 및 의심 환자에게 보조적 진단으로 사용되고 있다. 지질 친화성의 특성과 에탄올이 첨가된 약제의 특성상 주사 후 3-way Set에 잔량과 주사 시 환자의 통증이 관심의 대상이 된다. 본 연구는 효과적인 방사성의약품의 주사와 환자 케어 및 우수한 영상을 위함이다. 내원환자 70명을 대상으로 하였고, 환자들에게 평균 $259{\pm}74MBq$의 $^{18}F-FDG$ (20명), $^{18}F-FP-CIT$ (20명), $^{18}F-Florbetaben$ (30명)을 3-way Set으로 주사(Reflusing 2회, Reflusing 3회 이상)를 하여 주사 후 잔량을 측정하였고, $^{18}F-Florbetaben$ 주사 시 사용되는 3-way Set와 Heparin Cap의 효율적인 주사방법을 알아보기 위해서 주사 후 잔량을 측정하여 SPSS 12.0 ANOVA, t-test 통계분석을 통하여 잔량을 비교분석 하였다. 그리고 $^{18}F-Florbetaben$의 통증 유발 성분의 에탄올 양을 측정하기 위하여 Gas Chromatography로 추가 분석을 실시해보았다. Reflusing 2회 시 $^{18}F-FDG$: 1.48 MBq (0.04 mCi), $^{18}F-FP-CIT$: 7.4 MBq (0.2 mCi), $^{18}F-Florbetaben$: 32.6 MBq (0.88 mCi)의 잔량이 측정 되었고 Reflusing 3회 이상 시 $^{18}F-FDG$: 1.85 MBq (0.05 mCi), $^{18}F-FP-CIT$: 3.7 MBq (0.10 mCi), $^{18}F-Florbetaben$: 36.3 MBq(0.98 mCi)의 잔량이 측정 되었다. 다중 비교결과 Reflusing 2회 시 잔량이 유의미한 차이가 있었고(P < 0.05), 3회 이상 시 $^{18}F-Florbetaben$과 $^{18}F-FDG$, $^{18}F-FP-CIT$는 잔량의 유의미한 차이가 있었으며(P < 0.05), $^{18}F-FDG$와 $^{18}F-FP-CIT$는 유의미한 차이가 없었다(P > 0.05). $^{18}F-Florbetaben$ 주사 후 잔량은 3-way Set: 32.6 MBq (0.88 mCi), 36.3 MBq (0.98 mCi)였고 Heparin Cap: 7.03 MBq (0.19 mCi)으로 유의미한 차이가 있었다(P < 0.05). Gas Chromatography 분석결과 에탄올: 207665 ppm, 아세톤: 377.4 ppm으로 나타났다. $^{18}F-Florbetaben$은 $^{18}F-FDG$와 $^{18}F-FP-CIT$에 비해 주사 후 잔량이 많았고, 통증을 유발하는 에탄올 성분의 수치가 높게 나타났다. 주사 시 3-way Set 방식보다는 Heparin Cap을 사용함이 잔량 감소에 더 효과적이었다. 그리고 주사 시 환자의 통증 완화를 위해서 천천히 주사함을 권고한다.

• 대한방사성의약품학회지
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• 제7권2호
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• pp.153-159
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• 2021

This article provides an efficient ¹⁸F-labeling protocol based on a rapid condensation reaction between 2-cyanobenzothiazole (CBT) and N-terminal cysteine-containing biomolecules. The ¹⁸F-labeled CBT (¹⁸F-1) was prepared by radiofluorination of the tosylated precursor 4 with 18-crown-6/K+/[¹⁸F]F- complex. Using the purified ¹⁸F-1, ¹⁸F-labeled peptide (¹⁸F-7) and protein (¹⁸F-8) could be synthesized efficiently under mild conditions. This strategy would provide a convenient approach for rapid and site-specific ¹⁸F-labeling of various peptides and proteins for in vivo imaging and biomedical applications.

• 대한방사성의약품학회지
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• 제2권2호
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• pp.73-83
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• 2016

Imaging hypoxia using positron emission tomography (PET) is of great importance for cancer therapy. [$^{18}F$] Fluoromisonidazole (FMISO) was the first PET agent used for imaging tumor hypoxia. Various radiolabeled nitroimidazole derivatives such as [$^{18}F$]fluoroerythronitroimidazole (FETNIM), [$^{18}F$]1-${\alpha}$-D-(2-deoxy-2-fluoroarabinofuranosyl)-2-nitroimidazole(FAZA), 2-(2-nitroimidazol-1-yl)-N-(3,3,3-[18F]-trifluoropropyl)acetamide ([$^{18}F$]EF-3), [$^{18}F$]2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF-5), 3-[$^{18}F$]fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3,-triazol-1-yl)-propan-1-ol ([$^{18}F$]HX-4), and [$^{18}F$]fluoroetanidazole (FETA) were developed successively. However, these imaging agents still produce PET images with limited resolution; the lower blood flow in hypoxic tumors compared to normoxic tumors results in low uptake of the agents in hypoxic tumors. Thus, the development of better imaging agents is necessary.

• Bulletin of the Korean Chemical Society
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• 제33권7호
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• pp.2177-2180
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• 2012

New [$^{18}F$]F-fluorination methods using a minimized amount of precursor has been developed by controlling the base concentration. In the first method, pre-conditioning of the anion exchange cartridge with $K_2CO_3$ solution or water was carried out. The trapped [$^{18}F$]fluoride on the cartridge was then eluted by KOMs or KOTf solution. [$^{18}F$]F-Fluorination could be performed without additional base. In the second method, the QMA cartridge was preconditioned with KOMs solutions. Trapped [$^{18}F$]fluoride on the QMA was then eluted with KOMs and additional base, such as KOH, $K_2CO_3$, and $KHCO_3$, was added into the reaction vessel. Method 1 showed a [$^{18}F$]F-incorporation yield of 20.9% for [$^{18}F$]FLT synthesis with 5 mg of precursor. Unlike method 1, a [$^{18}F$]F-incorporation yield of 91.4% was achieved from the same amount of precursor in method 2.

• Korean Journal of Radiology
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• 제25권8호
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• pp.742-748
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• 2024

Objective: ¹⁸F-N-(2-(Diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy) picolinamide (¹⁸F-PFPN) is a novel positron emission tomography (PET) probe designed to specifically targets melanin. This study aimed to evaluate the diagnostic feasibility of ¹⁸F-PFPN in patients with ocular or orbital melanoma. Materials and Methods: Three patients with pathologically confirmed ocular or orbital melanoma (one male, two females; age 41-59 years) were retrospectively reviewed. Each patient underwent comprehensive ¹⁸F-PFPN and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET scans. The maximum standardized uptake value (SUV_max) of the lesion and the interference caused by background tissue were compared between ¹⁸F-PFPN and ¹⁸F-FDG PET imaging. In addition, the effect of intrinsic pigments in the uvea and retina on the interpretation of the results was examined. The contralateral non-tumorous eye of each patient served as a control. Results: All primary tumors (3/3) were detected using ¹⁸F-PFPN PET, while only two primary tumors were detected using ¹⁸F-FDG PET. Within each lesion, the SUV_max of ¹⁸F-PFPN was 2.6 to 8.3 times higher than that of ¹⁸F-FDG. Regarding the quality of PET imaging, the physiological uptake of ¹⁸F-FDG PET in the brain and periocular tissues limited the imaging of tumors. However, ¹⁸F-PFPN PET minimized this interference. Notably, intrinsic pigments in the uvea and retina did not cause abnormal concentrations of ¹⁸F-PFPN, as no anomalous uptake of ¹⁸F-PFPN was detected in the healthy contralateral eyes. Conclusion: Compared to ¹⁸F-FDG, ¹⁸F-PFPN demonstrated higher detection rates for ocular and orbital melanomas with minimal interference from surrounding tissues. This suggests that ¹⁸F-PFPN could be a promising clinical diagnostic tool for distinguishing malignant melanoma from benign pigmentation in ocular and orbital melanomas.

• 대한핵의학회지
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• 제30권4호
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• pp.532-540
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• 1996

목적 : 종양세포의 증식을 평가하기 위해 radiofluorinated ethyluracil (FEU)과 deoxyadenosine analogue(FAD)를 합성하여 종양의 영상화를 시도하였다. 대상 및 방법 : 5-(2-Fluoroethyl)uracil ([$^{18}F$]FEU)은 2, 4-dimethoxy-5-(2-hydroxyethyl) pyrimidine을 $K^{18}F$와 처리한 후 HBr로 가수분해하여 얻었으며 Fluorodeoxyadenosine은 adenosine의 triacetylated analogue를 $K^{18}F$와 처리하여 얻었다. 생물학적 조직분포는 유방암 세포(13762 NF, 100,000 cells per rat, im)를 쥐에 접종한 후 0.5, 1, 2 및 4시간에 주요장기를 적출하여 %ID/g을 측정하고 자가방사영상은 방사성의약품 투여 45분 후에 얻었다. PET 영상은 VX-2 종양을 접종한 가토를 이용하여 얻었다. In vitro cell proliferation assay는 사람의 말초단핵구를 이용하였다. 결 과 : In vitro assay상 ([$^{18}F$]FEU는 세포증식시 DNA/RNA에 결합함을 시사하였다. ([$^{18}F$]FAD와 ([$^{18}F$]FEU의 종양/비종양 방사능 섭취비는 시간경과에 따라 증가하였으며 ([$^{18}F$]FAD와 ([$^{18}F$]FEU를 이용한 자가방사영상과 ([$^{18}F$]FEU를 이용한 PET 영상에서 종양을 잘 관찰할 수 있었다. 결 론 : ([$^{18}F$]FAD 및 ([$^{18}F$]FEU를 이용하여 종양세포의 증식을 PET 영상에서 평가할 수 있으리라 사료된다.

• 대한임상검사과학회지
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• 제55권4호
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• pp.261-268
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• 2023

[¹⁸F]Fluorocholine은 임상에서 부갑상선 선종, 전립선암 및 간세포암 진단 등에 사용되는 PET용 콜린 방사성의약품이다. 본 연구에서는 고체상 추출 카트리지법을 방사성의약품 자동합성장치에 적용하여 [¹⁸F]fluorocholine을 제조하는 방법을 최적화하였다. [¹⁸F]Fluorocholine은 하나의 반응용기를 사용하여 두 단계 표지반응으로 합성하였으며, [¹⁸F]fluorocholine 합성과정 중 생성되는 불순물을 제거하기 위해 사용하는 SepPak^Ⓡ Silica 카트리지의 개수를 3개로 최적화하였고, 전구 물질인 DMAE를 10%로 희석하였을 때 가장 높은 방사화학적 수율을 획득 할 수 있었다. 또한 최종 생산된 [¹⁸F] fluorocholine 주사액은 유럽약전에 명시된 품질관리기준을 모두 만족하였다. 본 연구를 통해 쉽고 간편하게 사용할 수 있는 고체상 추출 카트리지를 사용하여 방사성의약품 자동합성장치에 최적화한 [¹⁸F]fluorocholine의 합성법은 임상 현장에 안정적으로 [¹⁸F]fluorocholine을 공급하는데 유용하게 사용될 것으로 사료된다.

• 핵의학기술
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• 제13권3호
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• pp.147-151
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• 2009

Purpose: 2-[$^{18}F$]Fluoro-2-deoxy-D-glucose ([$^{18}F$]FDG) particularly plays as a important role in Positron Emission Tomography (PET) imaging in nuclear medicine. Domestic [$^{18}F$]FDG auto synthesizers are installed in Seoul National University Bundang Hospital (SNUBH) at June 2008, these modules were known that it's synthetic yields were guaranteed in average $45{\pm}5%$ so far. To improve yields and convenience of domestic [$^{18}F$]FDG auto synthesizer, numerous trials in reaction time, base concentration, pressure and temperature were performed to increase [$^{18}F$]FDG yields. Materials and Methods: Several synthetic factors (temperature, time and pressure) and shortcoming were corrected based on many evaporation test. Syringe dispensing of tetra-butylammonium bicarbonate (TBAB) was replaced with micro pipette to prepare tetrabutyl ammonium fluoride salt ([$^{18}F$]TBAF). Troublesome refill of liquid nitrogen every 2 hours which was used to protect vacuum system was changed to charcoal cartridge, base guard filter. To monitor the volume of delivered $[^{18}O]OH_2$ from cyclotron by surveillance camera, we set up the volumetric vial on the cover of the module. In addition to, the recovery vial was added in [$^{18}F$]FDG production system to recover [$^{18}F$]FDG loss due to the leak of valve ($V_{13,14}$) in [$^{18}F$]FDG purification process. Results: When we used micro pipette for adding TBAB ($30\;{\mu}L$ in 12% $H_2O$ in acetonitrile), this quantitative dispensation has enabled to improve $5.5{\pm}1.7%$ residual fluorine-18 activity in fluorine separation cartridge compared to syringe adding. Besides, the synthetic yields of [$^{18}F$]FDG has increased $58{\pm}2.6%$ (n=19), $58{\pm}2.9%$ (n=14), $60%{\pm}2.5%$ (n=17) for 3 months. The life cycle of charcoal cartridge and base vacuum was 3 months prior to filling liquid nitrogen every 2 hours and additional side separator can prevent pump corrosion by organic solvent. After setting of volumetric indicator vial, the operator can easily monitor the total volume of irradiated $[^{18}O]OH_2$ from cyclotron. The recovery vial can be used for the stabilizer when an irregular [$^{18}F$]FDG loss was generated by the leak of valves ($V_{13,14}$). Conclusions: We has optimized appropriate synthetic conditions (temperature, time, pressure) in domestic [$^{18}F$]FDG auto synthesizer. In addition to, the remodeling with several accessories improve yields of domestic [$^{18}F$]FDG auto synthesizer with reliable reproducibility.

• Journal of Gastric Cancer
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• 제18권3호
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• pp.218-229
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• 2018

Purpose: This study investigated whether the metabolic avidity of primary tumors and/or metastatic lymph nodes (LNs) measured by $^{18}F$-fluorodeoxyglucose ($^{18}F-FDG$) positron emission tomography/computed tomography (PET/CT) was related to survival after surgery in patients with advanced gastric cancer (AGC). Materials and Methods: One hundred sixty-eight patients with AGC who underwent preoperative $^{18}F-FDG$ PET/CT and curative resection were included. The $^{18}F-FDG$ avidity of the primary gastric tumor and LNs was determined quantitatively and qualitatively. The diagnostic performance of $^{18}F-FDG$ PET/CT was calculated, and the prognostic significance of $^{18}F-FDG$ avidity for recurrence-free survival (RFS) and overall survival (OS) was assessed. Results: In all, 51 (30.4%) patients experienced recurrence, and 32 (19.0%) died during follow-up (median follow-up duration, 35 months; range, 3-81 months); 119 (70.8%) and 33 (19.6%) patients showed $^{18}F-FDG$-avid primary tumors and LNs, respectively. $^{18}F-FDG$ PET/CT showed high sensitivity (73.8%) for the detection of advanced pathologic T ($pT{\geq}3$) stage and high specificity (92.2%) for the detection of advanced pN (${\geq}2$) stage. $^{18}F-FDG$ avidity of LNs was significantly associated with RFS (P=0.012), whereas that of primary tumors did not show significance (P=0.532). Univariate and multivariate analyses revealed that $^{18}F-FDG$ avidity of LNs was an independent prognostic factor for RFS (hazard ratio=2.068; P=0.029). Conclusions: $^{18}F-FDG$ avidity of LNs is an independent prognostic factor for predicting RFS. Preoperative $^{18}F-FDG$ PET/CT can be used to determine the risk and prognosis of patients with AGC after curative resection.