• 방사선산업학회지
• /
• 제10권4호
• /
• pp.181-187
• /
• 2016

Selective ${\beta}_1$-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective ${\beta}_1$-antagonists including nebivolol have high binding affinity on ${\beta}_1$-adrenergic receptor, not ${\beta}_2$-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective ${\beta}_1$-blockers in clinically used ${\beta}_1$-blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective ${\beta}_1$-blocker. Nebivolol is $C_2$-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of $^{18}F$. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for $^{18}F$-aromatic substitution, was synthesized in moderate yield which was readily subjected to $^{18}F$-aromatic substitution to give $^{18}F$-labelled nebivolol.

• 한국방사선학회논문지
• /
• 제15권7호
• /
• pp.957-964
• /
• 2021

PET/CT 검사 시 사용되는 F-18은 양전자를 방출하는 방사성동위원소이며, 높은 에너지의 소멸감마선과 베타선은 방사선작업종사자의 피폭을 초래하는 원인이 된다. 본 연구에서는 핵의학과에서 근무하는 방사선작업종사자의 피폭선량 저감방안의 일환으로, F-18에 대한 Apron의 낮은 차폐 효율의 원인을 규명하고, 아크릴로 이중 차폐한 Apron의 실효성을 평가하였다. L-Block, Apron+아크릴, Apron, 아크릴+Apron, 아크릴 다섯 개의 차폐체를 이용하여 선량을 측정하고, 몬테카를로 시뮬레이션을 수행하여 경향성을 비교하였다. 그 결과, 아크릴로 이중 차폐한 Apron의 차폐율이 Apron 단독 차폐한 경우보다 약 4~8% 높은 차폐효과가 있는 것으로 나타났다. 사용자의 활동성에 크게 영향이 가지 않는 범위 안에서 적절한 두께의 아크릴로 이중 차폐한 개인방호복은 방사선 작업종사자의 피폭저감화에 도움을 줄 수 있을 것이다.

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

• 대한방사성의약품학회지
• /
• 제4권2호
• /
• pp.51-56
• /
• 2018

Azeotropic drying process is routinely applied to enhance nucleophilicity of $[^{18}F]$fluoride ion during the nucleophilic production of PET radiotracers; however, the drying process requires usually 15-25 min. Due to the high demand of employing fluorine-18 ($t_{1/2}=109.8min$) in PET radiopharmaceutical production, several research groups have focused on the method development, obviating tedious removal process of the residual target water ($[^{18}O]H_2O$) for $[^{18}F]$fluoride ion complex to be used in radiofluorination. Some development in radiofluorination in a mixed organic solvent system was demonstrated with various aliphatic substrates, but only kryptand as a phase transfer agent was utilized in the reported method. Here, we extend to investigate the development scope of applicability with basic alkyl ammonium salt as a phase transfer agent through the extensive elution efficiency study and radiofluorination outcome for aliphatic radiofluorination.

• 대한방사성의약품학회지
• /
• 제3권2호
• /
• pp.122-128
• /
• 2017

In the 2000s, there has been a significant advance on carbon-fluorine (C-F) bond formation reactions via transition metal mediated or catalyzed methods. Of course, for the past 10 years, transition metal catalysis improves C-F bond formation in terms of practicality and even can be applied to C-18F bond formation reaction. In this mini-review, we summarize various transition metal mediated or catalyzed fluorination reactions, which were developed in the mid-2000s.

• Nuclear Engineering and Technology
• /
• 제8권1호
• /
• pp.1-8
• /
• 1976

의료용 $^{18}$ F을 단시간내에 생산하기 위하여 반조분리(recoil separation), 알루미나 칼럼크로마토그래피, 증류등 지금까지 알려진 분리방법들을 검토하고 각각의 분리방법으로 얻은 생성물중의 잔사, ${\gamma}$ 방출불순물, 및 $^3$H 함량등을 결정하였다. 핵반조분리 생성물이나 알루미나 칼럼크로마토그래피에 의한 분리생성물은 순도면에서 증류 분리 생성물보다 좋지 못하였고 특히 천연탄산리티움을 표적으로 사용하는 경우는 증류법이 가장 효과적임을 알수 있었다. 천연 탄산리티움 7g을 중성자속밀도 1$\times$$10^{13}$n/$\textrm{cm}^2$/sec에서 3시간 중성자 조사하고 증류에 의해 $^{18}$ F를 정제함으로서 무담체 $^{18}$ 를 대략 2mCi 이상 (10mCi 이하)의 규모로 일상생산할 수 있으며 이때 정제에 소요되는 시간은 35~40분이다.

• 대한방사성의약품학회지
• /
• 제3권2호
• /
• pp.91-97
• /
• 2017

$^{18}F-THK-5351$ is a PET radiotracer to image the hyperphosphorylated tau fibrillar aggregates in human brain. This protocol describes the optimized radiosynthesis of $^{18}F-THK-5351$ using a commercial GE $TRACERlab^{TM}$ $FX_{FN}$ radiosynthesis module. $^{18}F-THK-5351$ was prepared by nucleophilic [$^{18}F$]fluorination from its protected tosylate precursors, (S)-(2-(2-methylaminopyrid-5-yl)-6-[[2-(tetrahydro-2H-pyran-2-yloxy)-3-tosyloxy]propoxy] quinolone(THK-5352), at $110^{\circ}C$ for 10 min in dimethyl sulfoxide, followed by deprotection with 1 N HCl. The average radiochemical yield of $^{18}F-THK-5351$ was $31.9{\pm}6.7%$(decay-corrected, n = 10), with molar activity of $198.1{\pm}33.9GBq/{\mu}mol$($5.4{\pm}0.9Ci/{\mu}mol$, n = 10). The radiochemical purity was determined to be above 98%. The overall production time including HPLC purification is approximately 70 min. This fully-automated protocol is validated for clinical use.

• Bulletin of the Korean Chemical Society
• /
• 제26권3호
• /
• pp.393-398
• /
• 2005

The stability constants for the diaza-18-crown-6 ethers 2-6 and alkali metal cations ($Na^+,\;K^+,\;Rb^+\;and\;Cs^+$) were determined using potentiometry in 95% methanol. For each metal ion the stability constants of the partiallyfluorinated ligands 3-6 were larger than that of the non-fluorinated ligand 2, which might reflect an interaction between fluorine atoms and alkali metal cations. The stability constant of the ligand 4 was larger than that of the ligand 5 for each metal cation tested. This finding was also supported by the results of cation-induced chemical shifts in $^1H-,\;^{19}F$-NMR and extraction experiment. The potentiometry and NMR results as well as the X-ray crystal structures revealed that the position and number of fluorine atoms in the benzyl side arms was crucial for the enhanced interaction between a ligand and an alkali metal.

• 대한방사성의약품학회지
• /
• 제4권2호
• /
• pp.57-64
• /
• 2018

${\omega}-[^{18}F]$-Fluorohexadecanoic acid (FHA) has been used for imaging of fatty acid metabolism of myocardium. To increase retention of radiolabeled fatty acid by blocking ${\beta}$-oxidation, methyl branched analogues have been used. In this experiment, we tried to synthesize 18F-labeled ${\alpha}-$, ${\beta}-$ and ${\omega}-FHA$ for imaging of the myocardial fatty acid metabolism. We synthesized ${\alpha}-$, ${\beta}-$ and ${\omega}$-mesylated methyl hexadecanoates and labeled with $^{18}F$ by reacting with $[^{18}F]$TBAF in acetonitrile at $80^{\circ}C$ for 10 min. Methyl ester group was removed by 1 M NaOH at $80^{\circ}C$ for 5 min. The yields of ${\alpha}-[^{18}F]$ and ${\omega}-[^{18}F]FHA$ were 25.5 and 45.5%, respectively [EOS]. However, ${\beta}-[^{18}F]FHA$ was not labeled at all due to a fast elimination reaction. The biodistribution study in ICR-mice showed that ${\omega}-[^{18}F]FHA$ has higher myocardial uptake and lower liver uptake than ${\alpha}-[^{18}F]FHA$. The electron-withdrawing effect of fluorine at ${\alpha}-$ position is believed to be the major factor affecting the biodistribution.

• 한국초전도ㆍ저온공학회논문지
• /
• 제8권1호
• /
• pp.15-18
• /
• 2006

A new precursor solution wilt low fluorine content was synthesized for MOD processing of coated conductors. In this study, the precursor solution for MOD processing was synthesized using F-free yttrium and copper precursor. It was shown that crack-free and uniform precursor films were formed after calcination in humidified oxygen atmosphere. Less than 2 hours were required to finish the calcination process. The relatively gradual weight loss during the calcination process is attributed to the feasibility of fast calcination profile. The calcined precursor film was converted to a YBCO film without any secondary phases after annealing in wet $Ar/O_2$ atmosphere. Fully converted film shows uniform microstructure and high critical current density. $(Jc=2.7MA/cm^2) $.