Evaluation of 99mTc-MAG3-2-nitroimidazole for hypoxic tumor imaging

Yun Sang Lee,Young Joo Kim,Jae Min Jeong 대한방사성의약품학회 2019 Journal of radiopharmaceuticals and molecular prob Vol.5 No.1

2-Nitroimidazole derivatives have been reported to accumulate in hypoxic tissue. We prepared a novel 99mTc-MAG3-2-nitroimidazole and evaluated the feasibility for hypoxia imaging agent. Bz-MAG3-2-nitroimidazole wassynthesized by direct coupling of Bz-MAG3 and 2-nitroimidazole using dicyclohexylcarbodiimide. Bz-MAG3-2-nitroimidazole was labeled with 99mTc in the presence of tartaric acid and SnCl2-2H2O at 100°C for 30 min. And the reaction mixture was purified by C18 Sep-pak cartridge. The labeling efficiency and the radiochemicalpurity were checked by ITLC-SG/acetonitrile. The tumor was grown in balb/c mice for 8~13 days after thesubcutaneous injection of tumor cells, CT-26 (murine colon adenocarcinoma cell). Biodistribution study andtumor autoradiography were performed in the xenografted mice after i.v injection of 74 kBq/0.1 mL and 19MBq/0.1 mL of 99mTc-MAG3-2-nitroimidazole, respectively. In vivo images of 99mTc-MAG3-2-nitroimidazolein tumor bearing mice were obtained 1.5 hr post injection. The labeling efficiency was 45±20% and theradiochemical purity after purification was over 95%. Paper electrophoresis confirmed negative charge of99mTc-MAG3-2-nitroimidazole. 99mTc-MAG3-2-nitroimidazole was very stable at room temperature and its proteinbinding was 53%. The 99mTc-MAG3-2-nitroimidazole exhibited high uptake in the liver, stomach and intestine. In biodistribution study using tumor bearing mice, the uptakes (% ID/g) of the tumor were 0.5±0.1, 0.4±0.0,0.2±0.1 and 0.1±0.1 at 5, 15, 30 min and 4 hrs. Tumor/muscle ratio were 1.4±0.1, 2.2±0.83, 3.0±0.9, and 3.7(n=2) for 5, 15, 30 min and 4 hrs. The uptake in hypoxic area was found higher than in non-hypoxic area oftumor tissue by autoradiography. In vivo images showed the relatively faint uptake to the hypoxic tumor region. 99mTc-MAG3-2-nitroimidazole was successfully synthesized and found feasible for imaging hypoxia

Synthesis and biodistribution of 18F-labeled α-, β- and ω-fluorohexadecanoic acid

Yun-Sang Lee,Young Joo Kim,Gi Jeong Cheon,Jae Min Jeong 대한방사성의약품학회 2018 Journal of radiopharmaceuticals and molecular prob Vol.4 No.2

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

Microfluidic generation of Prussian blue-laden magnetic micro-adsorbents for cesium removal

Kang, Sung-Min,Rethinasabapathy, Muruganantham,Hwang, Seung Kuy,Lee, Go-Woon,Jang, Sung-Chan,Kwak, Cheol Hwan,Choe, Sang-Rak,Huh, Yun Suk Elsevier 2018 CHEMICAL ENGINEERING JOURNAL -LAUSANNE- Vol.341 No.-

<P><B>Abstract</B></P> <P>Here, we designed and synthesized a recoverable multifunctional adsorbent using a microfluidic reaction system and evaluated the removal performance of the smart adsorbent toward radioactive cesium as a model sample. Prussian blue-laden magnetic micro-adsorbents (PB-MNPs-MAs) with uniform morphology and monodispersity were generated via two-step sequential procedures using a glass capillary microfluidic system, followed by chemical co-precipitation with a high production rate. The cesium removal efficacy of the PB-MNPs-MAs was analyzed based on Langmuir and Freundlich isotherms by controlling adsorption parameters such as adsorbent size, initial cesium concentration, and contact time. The adsorption isotherm of the PB-MNPs-MAs was better fitted to the Langmuir model with a maximum cesium adsorption capacity of 58.73 mg g<SUP>−1</SUP>, which was 40% higher than that of macro-adsorbents in a dynamic magnetic field. This result can be attributed to their large specific area, which increased the kinetic rate of cesium adsorption and achieved saturation within 20 min. Additionally, the PB-MNPs-MAs were recovered from wastewater within 5 s under a static magnetic field, indicating their great potential for magnetic actuation. We believe that our PB-MNPs-MAs can encapsulate nano-functional adsorbents and prevent actuation, making them promising for environmental remediation and especially for removal of radionuclides.</P> <P><B>Highlights</B></P> <P> <UL> <LI> PB-MNPs-MAs were generated in microfluidic device using chemical co-precipitation. </LI> <LI> The prepared PB-MNPs-MAs are monodispersed with uniform morphology. </LI> <LI> PB-MNPs-MAs exhibited high Cs adsorption capacity (58.73 mg g<SUP>−1</SUP>). </LI> <LI> 100% recovery of PB-MNPs-MAs is possible under static magnetic field after Cs adsorption. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A study of ^99mTc-sestamibi labeling condition using radio-chromatography

Moon, Sung-Hyun,Lee, Yun-Sang,Lee, Dong Soo,Chung, June-Key,Jeong, Jae Min Korean Society of Radiopharmaceuticals and Molecul 2017 Journal of radiopharmaceuticals and molecular prob Vol.3 No.1

Tc-99m labeled sestamibi ($^{99m}Tc$-MIBI) is one of most widely used radiopharmaceuticals for myocardial SPECT imaging. Radiolabeling of $^{99m}Tc$-MIBI is recommended by heating in $100^{\circ}C$ water bath for 15 min. However, the water bath might be a source of contamination. Thus, if radiolabeling of $^{99m}Tc$-sestamibi can be performed at room temperature, then it would be more convenient to use in clinical application. In this study, we performed the radiolabeling of $^{99m}Tc$-MIBI in different temperature conditions or using different instruments to find out the efficient labeling condition. We studied the $^{99m}Tc$-MIBI labeling at room temperature or $100^{\circ}C$ heating block, and checked the labelling yields every 1 min for 10 min using radio-TLC with 2 different eluents-saline and acetone. From the experiment, we confirmed that the $^{99m}Tc$-MIBI can be labeled over 90% yield but not completed at room temperature. However, the $^{99m}Tc$-MIBI labeling was completed when it was performed in the $100^{\circ}C$ heating block. Finally, we proved that heating is essential for complete $^{99m}Tc$-MIBI labelling, furthermore using heating block is also possible instead of water bath.

생체흡착, 탈착 및 회화를 이용한 시안 용액으로부터 금의 회수

배민아(Min A Bae),곽인섭(In-Seob Kwak),원성욱(Sung Wook Won),윤영상(Yeoung-Sang Yun) 한국청정기술학회 2010 청정기술 Vol.16 No.2

Evaluation of ^99mTc-MAG₃-2-nitroimidazole for hypoxic tumor imaging

Lee, Yun-Sang,Kim, Young Joo,Jeong, Jae Min Korean Society of Radiopharmaceuticals and Molecul 2019 Journal of radiopharmaceuticals and molecular prob Vol.5 No.1

2-Nitroimidazole derivatives have been reported to accumulate in hypoxic tissue. We prepared a novel $^{99m}Tc-MAG_3$-2-nitroimidazole and evaluated the feasibility for hypoxia imaging agent. $Bz-MAG_3$-2-nitroimidazole was synthesized by direct coupling of $Bz-MAG_3$ and 2-nitroimidazole using dicyclohexylcarbodiimide. $Bz-MAG_3$-2-nitroimidazole was labeled with $^{99m}Tc$ in the presence of tartaric acid and $SnCl_2-2H_2O$ at $100^{\circ}C$ for 30 min. And the reaction mixture was purified by $C_{18}$ Sep-pak cartridge. The labeling efficiency and the radiochemical purity were checked by ITLC-SG/acetonitrile. The tumor was grown in balb/c mice for 8~13 days after the subcutaneous injection of tumor cells, CT-26 (murine colon adenocarcinoma cell). Biodistribution study and tumor autoradiography were performed in the xenografted mice after i.v injection of 74 kBq/0.1 mL and 19 MBq/0.1 mL of $^{99m}Tc-MAG_3$-2-nitroimidazole, respectively. In vivo images of $^{99m}Tc-MAG_3$-2-nitroimidazole in tumor bearing mice were obtained 1.5 hr post injection. The labeling efficiency was $45{\pm}20%$ and the radiochemical purity after purification was over 95%. Paper electrophoresis confirmed negative charge of $^{99m}Tc-MAG_3$-2-nitroimidazole. $^{99m}Tc-MAG_3$-2-nitroimidazole was very stable at room temperature and its protein binding was 53%. The $^{99m}Tc-MAG_3$-2-nitroimidazole exhibited high uptake in the liver, stomach and intestine. In biodistribution study using tumor bearing mice, the uptakes (% ID/g) of the tumor were $0.5{\pm}0.1$, $0.4{\pm}0.0$, $0.2{\pm}0.1$ and $0.1{\pm}0.1$ at 5, 15, 30 min and 4 hrs. Tumor/muscle ratio were $1.4{\pm}0.1$, $2.2{\pm}0.83$, $3.0{\pm}0.9$, and 3.7 (n=2) for 5, 15, 30 min and 4 hrs. The uptake in hypoxic area was found higher than in non-hypoxic area of tumor tissue by autoradiography. In vivo images showed the relatively faint uptake to the hypoxic tumor region. $^{99m}Tc-MAG_3$-2-nitroimidazole was successfully synthesized and found feasible for imaging hypoxia.

과산화수소 증기를 이용한 유사화학작용제의 제독

김윤기 ( Yun Ki Kim ),유현상 ( Hyun Sang Yoo ),김민철 ( Min Cheol Kim ),황현철 ( Hyun Chul Hwang ),류삼곤 ( Sam Gon Ryu ),이해완 ( Hae Wan Lee ) 한국화학공학회 2014 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.52 No.3

Vapor-phase hydrogen peroxide(VPHP) has been used as a sterilant in the field of medical and pharmaceuticalapplication due to low corrosive than chlorine contained sterilant. In addition, it is well known that VPHP iseffective for decontamination of chemical warfare agents by adding ammonia gas. In this study, the decontaminationefficiency was confirmed about CEPS, DFP and dimethoate as simulants of HD, GD and VX using VPHP respectively. For this purpose, VPHP generated from self configured device was injected into decontamination chamber and maintainedfor reaction time. After the decontamination, the residues are analyzed by GC/MS and decontamination efficiencywas calculated. Through by-product for each simulants, the similarities in reaction mechanism of chemicalwarfare agents were confirmed. CEPS was completely decontaminated at 30% relative humidity within 60 min. By addingammonia gas, DFP and dimethoate were completely decontaminated within 30 and 150 min respectively.

Synthesis and biodistribution of ¹⁸F-labeled α-, β- and ω-fluorohexadecanoic acid

Lee, Yun-Sang,Kim, Young Joo,Cheon, Gi Jeong,Jeong, Jae Min Korean Society of Radiopharmaceuticals and Molecul 2018 Journal of radiopharmaceuticals and molecular prob Vol.4 No.2

${\omega}-[^{18}F]$-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.

측정 자세의 변화에 따른 맥의 변화 특성: 선 자세, 앉은 자세, 누운 자세

권선민 ( Sun Min Kown ),강희정 ( Hee Jung Kang ),이상훈 ( Sang Hun Lee ),임윤경 ( Yun Kyoung Yim ),이용흠 ( Yong Heum Lee ) 대한경락경혈학회 2009 Korean Journal of Acupuncture Vol.26 No.4

Objectives: Informations on pulse diagnosis in literature are based on diagnosing pulse waveforms on supine posture. However, today`s pulse waveforms are measured on various postures for the convenience of patients or doctors. For objective measurement, the effect of posture on the pulse waveforms should be considered. The objective of this study was to find posture-related changes in the radial pulse waveforms. Methods: We used an instrument, DMP-3000(DAEYOMEDI Co., Ansan, Korea), measuring radial pulse waveforms noninvasively by tonometric method. 25 male subjects participated in the trial. Before measuring radial pulse waveforms subjects had rest for 5 min. The pulse waveforms were measured on the left wrist. Each subject underwent this course on the supine, sitting, and standing posture. We analyzed pulse waveforms with Height-parameters, Time-parameters, Energy, and Elastic rate. Results: Height-parameters(h1~h5) on the supine posture were bigger than those on the sitting and standing posture. In case of Time-parameters, the parameters making up systolic time decrease in order of on standing, sitting, and supine position. However, systolic time and diastolic time didn`t have any changes. Energy of pulse was the biggest on supine posture and Elastic rate on standing posture. Conclusions: In this study we found that posture changes affect radial pulse waveforms. For quantification of the changes, more trials should be done. After analyzing much data we might apply parameters of pulse waveforms changed by posture. Also, we might diagnose special disease with properties of pulse waveforms by posture.

Antinociceptive profiles and mechanisms of orally administered coumarin in mice.

Park, Soo-Hyun,Sim, Yun-Beom,Kang, Yu-Jung,Kim, Sung-Su,Kim, Chea-Ha,Kim, Su-Jin,Lim, Su-Min,Suh, Hong-Won Pharmaceutical Society of Japan 2013 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.36 No.6

<P>In the present study, the antinociceptive profiles of coumarin were examined in ICR mice. Coumarin administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of coumarin maintained at least for 60 min. But, the cumulative response time of nociceptive behaviors induced by a subcutaneous (s.c.) formalin injection, intrathecal (i.t.) substance P (0.7 ?g) or glutamate (20 ?g) injection was not affected by coumarin. In addition, intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration with coumarin (10-40 ?g) attenuated acetic acid-induced writhing response in a dose dependent manner. Intraperitoneal (i.p.) pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by coumarin in the writhing test. Furthermore, i.c.v. or i.t. pretreatment with naloxone (5 ?g) reversed the decreased acetic acid-induced writhing response. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an α2-adrenergic receptor antagonist) did not affect antinociception induced by coumarin in the writhing test. Our results suggest that coumarin exerts a selective antinociceptive property in the acetic acid-induced visceral-derived pain model. Furthermore, the antinociceptive effect of coumarin may be mediated by activation of central opioid receptors, but not serotonergic and adrenergic receptors.</P>