• Bulletin of the Korean Chemical Society
• /
• 제32권1호
• /
• pp.71-76
• /
• 2011

An efficient nucleophilic [$^{18}F$]fluorination has been studied to reduce byproducts and preparation time. Instead of conventional aqueous solution of $K_2CO_3-K_{222}$, several organic solution containing inert organic salts were used to release [$^{18}F$]fluoride ion and anion bases captured in the polymer cartridge, concluding that methanol solution is the best choice. Comparing to azeotropic drying process, one min was sufficient to remove methanol completely, resulting in about 10% radioactivity saving by reducing drying time. The polymer cartridge, Chromafix$^{(R)}$ (PS-$HCO_3$) was pretreated with several anion bases to displace pre-loaded bicarbonate base. Phosphate bases showed better results than carbonate bases in terms of lower basicity. tert-Butanol solvent used as a reaction media played another critical role in nucleophilic [18F]fluorination by suppressing eliminated side product. Consequent [$^{18}F$]fluorination under the present condition afforded fast preparation of reaction solution and high radiochemical yields (98% radio-TLC, 84% RCY) with 94% of precursor remained.

• 대한방사성의약품학회지
• /
• 제5권2호
• /
• pp.145-151
• /
• 2019

Fluorine-18 is considered to be the radionuclide of choice for positron emission tomography (PET). Thus, the development of small molecule-based radiopharmaceuticals for use in diagnostic imaging relies heavily on efficient radiofluorination techniques. Until the early 2000s, diaryliodonium salts and aryliodonium ylides were widely employed as labeling precursors to yield aromatic PET radiotracers with cyclotron-produced [¹⁸F]fluoride ion. Rapid recent progress in the development of efficient borylation methods has led to a paradigm shift in ¹⁸F-labeling methods. In addition, deoxyfluorination has attracted a great deal of interest as an alternative approach to aryl ring activation with ¹⁸F^-. In this review, methods for radiolabel development are discussed with a specific focus on the progress made in the last 5 years. Other interesting ¹⁸F-based protocols are also briefly introduced. New methods for exploiting ¹⁸F^- are expected to increase the number of ¹⁸F-labeling methods, to allow applications in a range of chemical environments.

• 대한방사성의약품학회지
• /
• 제7권1호
• /
• pp.22-32
• /
• 2021

Fluorine-18 is by far the most widely exploited radionuclide in PET (positron emission tomography) radiochemistry. The physical half-life of fluorine-18 allows for chemical manipulation within a restricted timeframe, and cyclotron-produced fluoride ion has been widely applied in aliphatic and aromatic nucleophilic radiofluorinations to produce a variety of established radiotracers. Radiotracers have become more structurally complicated to address diverse targets in physiobiological systems. There is therefore an unmet need to complement traditional C-¹⁸F bond-forming radiofluorination with new and efficient radiolabeling techniques to tackle the myriad of possible chemical environments. This review discusses recent advances in organometallic fluorine-18 bond creation in ¹⁸F-radiochemistry. Although not widely employed, new radiolabeling strategies for constructing boron-¹⁸F, silicon-¹⁸F, aluminum-¹⁸F, and other metal-¹⁸F bonds are described in view of their potential use in the development of novel radiopharmaceuticals.

• 대한방사성의약품학회지
• /
• 제3권1호
• /
• pp.3-14
• /
• 2017

Nucleophilic aromatic fluorination has been one of the most explored methods in fluorin-18 based radiochemistry. Unlike electrophilic $[^{18}F]$fluorination methods, no-carrier-added nucleophilic radiofluorination with cyclotron-produced $[^{18}F]$fluoride ion offers better specific radioactivity which is essential aspect to obtain good quality images from positron emission tomography. Contrary to amenable aliphatic radiofluorination, the development of reliable aromatic $[^{18}F]$fluorination methods has been pursued by many research groups; however, no viable method has yet been established. Recently, hypervalent iodine compound draws increasing attention as versatile radiolabeling precursor for various $[^{18}F]$fluoroarenes, since it bears the capacity to introduce fluorine-18 either on electron-deficient or electron-rich aryl ring with enhanced regiospecificity. Other classes of hypervalent iodine congeners often utilized in radiochemistry are iodylarenes, iodonium ylides, and spirocyclic iodonium ylides. Recently developed spirocyclic iodonium ylides have already been avidly employed to provide various $[^{18}F]$aryl fluorides with high labeling efficiency. This metal-free protocol would afford efficient routes, replacing the traditional approaches to $[^{18}F]$fluoroarenes, from prosthetic labeling synthons to complex PET radiotracers.

• 대한방사성의약품학회지
• /
• 제8권2호
• /
• pp.63-70
• /
• 2022

The development of myocardial perfusion imaging (MPI) agents has been motivated because coronary artery disease has been one of the leading causes of death worldwide since the 1960s. Several positron emission tomography (PET) MPI agents were developed, and ¹⁸F-labeled phosphonium cations were reported actively among them. In this study, we synthesized novel ¹⁸F-labeled phosphonium cations, (5-[¹⁸F]fluoropentyl)diphenyl(pyridin-2-yl)phosphonium and (2-(2-[¹⁸F]fluoroethoxy)ethyl)diphenyl(pyridin-2-yl)phosphonium, and evaluated potential as MPI agents. Two labeled compounds were synthesized via nucleophilic substitution reactions of ¹⁸F-fluoride with the appropriate tosylate precursor in the presence of Kryptofix 2.2.2 and K₂CO₃. MicroPET studies were performed in normal rats to evaluate in vivo distribution of radiolabeled phosphonium cations for 60 min. The radiolabeled compounds were synthesized with 5%-10% yield. The radiochemical purity of labeled compounds was > 98% by analytical HPLC, and the specific activity was > 11.8 GBq/µmol. The result of microPET studies of these labeled compounds in rats showed intense uptake in the myocardium at 30 and 60 min. The results suggest that these ¹⁸F-labeled novel phosphonium cations would have potential as promising candidates for myocardial perfusion imaging.

• 대한핵의학회지
• /
• 제28권3호
• /
• pp.331-337
• /
• 1994

In order to develop a $^{18}F$-labelled myocardial perfusion agent(flow tracer) for PET, $^{18}F$-labelled organic ammonium cations were synthesized and evaluated in relation to their biodistribution. Five quaternary organic ammonium compounds were labelled with $^{18}F$ in a side chain with moderate to good yields by direct introduction of $^{18}F$-fluoride. Radiochemical yields have been achieved in 30-40min by the precursors (tosylates) in dimethylsulfoxide 15-60% (decay corrected). The reaction was found to be autocatalyzed. A remote controlled procedure was developed in these synthesis. $^{18}F$-Labelling and HPLC-purification of com-pounds needed about 60 min(Yield; 7-20%). Up to now the two compounds N-4-[$^{18}F$]fluorobutyl-pyridinium cation(1) and N, N dibenzyl-4(2-[$^{18}F$]fluoroethyl)piperidinium cation(2) were investigated in relation to their biodistribution in mice. Compound 1 showed at 1 min post injection the high uptake of 19.22% ID/g organ in the myocardium but a following fast decline to 1.12% ID/g organ after 40min. Uptake of compound 2 was after 1min in the heart 5.90% ID/g organ but after 40min at the relative high value of 4.33% ID/g organ. Heart:blood ratio for compound(1) at 1 min was 8.3, at 40 min 2.6 for compound II 2.0(1min) and 15.0(40 min). As data of compound 2 showed greater heart uptake, slower myocardial release, and higher heart: blood ratios, compound 2 is a good candidate for further evaluation.

• Journal of Cardiovascular Imaging
• /
• 제31권3호
• /
• pp.145-149
• /
• 2023

BACKGROUND: ¹⁸F-sodium fluoride positron emission tomography/computed tomography (¹⁸F-NaF PET/CT) has been proven to be useful in identification of microcalcifications, which are stimulated by inflammation. Blood speckle imaging (BSI) is a new imaging technology used for tracking the flow of blood cells using transesophageal echocardiography (TEE). We evaluated the relationship between turbulent flow identified by BSI and inflammatory activity of the aortic valve (AV) as indicated by the ¹⁸F-NaF uptake index in moderate aortic stenosis (AS) patients. METHODS: This study enrolled 18 moderate AS patients diagnosed within the past 6 months. BSI within the aortic root was acquired using long-axis view TEE. The duration of laminar flow and the turbulent flow area ratio were calculated by BSI to demonstrate the degree of turbulence. The maximum and mean standardized uptake values (SUVmax, SUVmean) and the total microcalcification burden (TMB) as measured by ¹⁸F-NaF PET/CT were used to demonstrate the degree of inflammatory activity in the AV region. RESULTS: The mean SUVmean, SUVmax, and TMB were 1.90 ± 0.79, 2.60 ± 0.98, and 4.20 ± 2.18 mL, respectively. The mean laminar flow period and the turbulent area ratio were 116.1 ± 61.5 msec and 0.48 ± 0.32. The correlation between SUVmax and turbulent flow area ratio showed the most positive and statistically significant correlation, with a Pearson's correlation coefficient (R²) of 0.658 and a p-value of 0.014. CONCLUSIONS: The high degree of trans-aortic turbulence measured by BSI was correlated with severe AV inflammation.

• 대한핵의학회지
• /
• 제29권4호
• /
• pp.533-540
• /
• 1995

정량적인 PET 영상에서는 감쇠보정이 매우 중요하며 가장 정확한 방법은 투과스캔을 관심부위에 실시하여 측정된 감쇠보정영상을 만들고, 이를 같은 부위에서 실시한 방출 영상의 재구성에 적용하는 것이다. 기존의 방법은 투과스캔 후에 추적자가 섭취되기까지 장시간이 경과된 후 방출스캔을 하므로 PET스캐너의 효율적 사용에 제한이 있었다. 따라서, 스캔시간을 단축하고 촬영중 환자가 움직일 가능성을 최소화시켜 영상의 질을 개선하고 PET스캐너의 효율을 높이기 위하여, 추적자를 주사한 후 투과 및 방출스캔을 동시에 실시하여, 투과스캔에서의 측정치를 왜곡시키는 방출계수를 빼주는 T+E 감쇠보정 방법을 실행하였다. 배후에는 F-l8 fluoride ion $0.4{\mu}Ci/cc$의 방사능을 가진 물을 실린더 모형(5750 cc)에 채우고, 목적물을 나다내는 1개의 삽입물 실린더(276 cc)에는 F-18 fluoride ion $4.3{\mu}Ci/cc$의 방사능을 주입하고 공기를 주입한 삽입물 실린더와 테플론으로 이루어진 삽입물 실린더를 사용하여 T+E 방법의 특성을 고찰하였다. 투과용선원으로 Ge-68(10 mCi) 회전 핀선원을 사용하여 5시간 동안에 T+E 스캔을 5분, 10분, 20분, 방출스캔을 20분씩 교대로 5차례 실행하여 투과 및 방출영상이 최종 방출영상에 미치는 오차를 측정하였다. T+E 스캔으로 감쇠보정한 방출영상과 기준 투과영상으로 감쇠보정한 방출영상을 비교하면, 목적물의 방사능이 $1.0{\mu}Ci/cc$일 경우 T+E 감쇠보정 방법의 오차는 2.6%이었으며 이 오차는 목적물의 방사능이 줄어들수록 더욱 감소하였다. 또한, T+E 방법으로 구성된 방출영상의 노이즈는 기준 투과스캔 방법으로 보정된 영상에 비하여 유의한 차이를 보이지 않았다. 그러므로, 회전 핀선원과 투과 및 방출 동시 영상 방법을 사용하여 정확한 감쇠보정을 할 수 있었으며 이 방법은 임상 PET 영상에서 환자당 스캔시간을 줄임으로써, 환자의 움직임으로 인하여 발생할 수 있는 오차를 최소화하여 PET 스캐너의 효율을 높일 수 있었다.

• 대한핵의학회지
• /
• 제33권6호
• /
• pp.527-536
• /
• 1999

목적: [C-11]flumazenil (RO 15-1788)은 벤조디아제핀 수용체 영상용 방사성 의약품으로 여러 가지신경, 정신 질환에서 양전자방출촬영(PET)용으로 연구되고 있다. 이 연구에서는2-amino 5-fluoroben-zoic acid를 출발물질로 사용하여 5단계에 걸쳐 플루마제닐 유도체를 합성한 후 F-18으로 표지하여 실험 동물에서의 성체 내 분포를 보았다. 대상 및 방법: 플루마제닐(c)의 합성은 F Hoffmann-La-Ro-che (Basle/CH)에서 보고된 방법에 의해 수정하여 합성하였다. 플루마제닐 유도체(d)는 플루마제닐(c)의 C-3 곁가지의 ethylester기를 tetrabutylammonium hydroxide와 반응하여 가수분해한 후 ditosylethane을 사용하여 tosyl기를 도입하여 합성하였다. 3-(2-[F-18]fluoro)flumazenil(e)의 합성은 TR-l3 사이클로트론에서 제조한 [F-18fluoride를 acetonitrile 용매하에서 플루마제닐 유도체(d)와 친핵성 치환반응으로 표지하였다. 표지된 플루마제닐 유도체는 TLC로 표지 효율을 측정하고, alumina-N과 $C_{18}$ Sep-pak으로 정제하였다. 3-(2-[F-18]fluoro)flumazenil의 생체 내 분포를 보기 위해 마우스(n=9)의 꼬31정맥으로 3-(2-[F-18]fluoro)flumazenil (0.37 MBq/0.1 mL)을 주사한 후 10, 30, 60분 후에 희생시켰다. 각 장기별 무게를 측정한 후 감마카운터로 방사능을 계수하였다. 투여한 방사능 양과 장기 내 방사능치를 구하여 시간에 따른 장기의 단위 무게별 주사량 대비 백분율(% ID/g)을 계산하였다. 결과: 플루마제닐 유도체 합성(d)의 전체 수득률은 40%였고, 플루마제닐 유도체의 F-18 표지효율은 66% 이상이었다. 마우스를 이용한 생체분포 실험에서 뇌의 섭취율은 10, 30, 60분에서 $2.5{\pm}0.4,\;2.2{\pm}0.3,\;2.1{\pm}0.1%ID/g$이었고, 혈액은 $3.7{\pm}0.4,\;3.3{\pm}0.1,\;3.3{\pm}0.09%ID/g$이었다. 결론: 새로운 벤조디아제 핀 수용체 영상용 방사성 의약품으로서 3-(2-[F-18]fluoro) flumazenil을 높은 표지 효율로 합성함으로서 PET와 SPECT 영상의 비교 연구에 이용될 수 있으며, F-18을 플루마제닐 유도체의 제각기 다른 위치에 치환함으로서 체내동태에 대한 연구에도 이용될 수 있다.

• 핵의학기술
• /
• 제13권3호
• /
• pp.147-151
• /
• 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.