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Ayoung Pyo,Jung-Joon Min,김동연 대한방사성의약품학회 2022 Journal of radiopharmaceuticals and molecular prob Vol.8 No.2
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.
Kim, Dong-Yeon,Kim, Hyeon Sik,Reder, Sybille,Zheng, Jin Hai,Herz, Michael,Higuchi, Takahiro,Pyo, AYoung,Bom, Hee-Seung,Schwaiger, Markus,Min, Jung-Joon Society of Nuclear Medicine 2015 The Journal of nuclear medicine Vol.56 No.10
<P>Despite substantial advances in the diagnosis of cardiovascular disease, there is a need for <SUP>18</SUP>F-labeled myocardial perfusion agents for the diagnosis of ischemic heart disease because current PET tracers for myocardial perfusion imaging have a short half-life that limits their widespread clinical use in PET. Thus, <SUP>18</SUP>F-labeled fluoroalkylphosphonium derivatives (<SUP>18</SUP>F-FATPs), including (5-<SUP>18</SUP>F-fluoropentyl)triphenylphosphonium cation (<SUP>18</SUP>F-FPTP), (6-<SUP>18</SUP>F-fluorohexyl)triphenylphosphonium cation (<SUP>18</SUP>F-FHTP), and (2-(2-<SUP>18</SUP>F-fluoroethoxy)ethyl)triphenylphosphonium cation (<SUP>18</SUP>F-FETP), were synthesized. The myocardial extraction and image quality of the <SUP>18</SUP>F-FATPs were compared with those of <SUP>13</SUP>N-NH<SUB>3</SUB> in rat models. <B>Methods:</B> The first-pass extraction fraction (EF) values of the <SUP>18</SUP>F-FATPs (<SUP>18</SUP>F-FPTP, <SUP>18</SUP>F-FHTP, <SUP>18</SUP>F-FETP) and <SUP>13</SUP>N-NH<SUB>3</SUB> were measured in isolated rat hearts perfused with the Langendorff method (flow velocities, 0.5, 4.0, 8.0, and 16.0 mL/min). Normal and myocardial infarction rats were imaged with small-animal PET after intravenous injection of 37 MBq of <SUP>18</SUP>F-FATPs and <SUP>13</SUP>N-NH<SUB>3.</SUB> To determine pharmacokinetics, a region of interest was drawn around the heart, and time–activity curves of the <SUP>18</SUP>F-FATPs and <SUP>13</SUP>N-NH<SUB>3</SUB> were generated to obtain the counts per pixel per second. Defect size was analyzed on the basis of polar map images of <SUP>18</SUP>F-FATPs and <SUP>13</SUP>N-NH<SUB>3.</SUB> <B>Results:</B> The EF values of <SUP>18</SUP>F-FATPs and <SUP>13</SUP>N-NH<SUB>3</SUB> were comparable at low flow velocity (0.5 mL/min), whereas at higher flows EF values of <SUP>18</SUP>F-FATPs were significantly higher than those of <SUP>13</SUP>N-NH<SUB>3</SUB> (4.0, 8.0, and 16.0 mL/min, <I>P</I> < 0.05). Myocardium-to-liver ratios of <SUP>18</SUP>F-FPTP, <SUP>18</SUP>F-FHTP, <SUP>18</SUP>F-FETP, and <SUP>13</SUP>N-NH<SUB>3</SUB> were 2.10 ± 0.30, 4.36 ± 0.20, 3.88 ± 1.03, and 0.70 ± 0.09, respectively, 10 min after injection, whereas myocardium-to-lung ratios were 5.00 ± 0.25, 4.33 ± 0.20, 7.98 ± 1.23, and 2.26 ± 0.14, respectively. Although <SUP>18</SUP>F-FATPs and <SUP>13</SUP>N-NH<SUB>3</SUB> sharply delineated myocardial perfusion defects, defect size on the <SUP>13</SUP>N-NH<SUB>3</SUB> images was significantly smaller than on the <SUP>18</SUP>F-FATP images soon after tracer injection (0–10 min, <I>P</I> = 0.027). <B>Conclusion:</B> <SUP>18</SUP>F-FATPs exhibit higher EF values and more rapid clearance from the liver and lung than <SUP>13</SUP>N-NH<SUB>3</SUB> in normal rats, which led to excellent image quality in a rat model of coronary occlusion. Therefore, <SUP>18</SUP>F-FATPs are promising new PET radiopharmaceuticals for myocardial perfusion imaging.</P>
Jang, Hwa Youn,Kwon, Seong Young,Pyo, Ayoung,Hur, Min Goo,Kim, Sang Wook,Park, Jeong-Hoon,Kim, Hee-Jung,Yang, Seung Dae,Lee, Sunwoo,Kim, Dong-Yeon,Min, Jung-Joon Chapman and Hall in association with the British N 2015 Nuclear medicine communications Vol.36 No.1
<▼1><P>Supplemental Digital Content is available in the text.</P></▼1><▼2><P>[<SUP>11</SUP>C]Acetate, a radiotracer for PET imaging, is a promising radiopharmaceutical for overcoming the limitation of 2-deoxy-2-[<SUP>18</SUP>F]fluoro-<SMALL>D</SMALL>-glucose in a number of cancers. Here, the optimized automatic synthesis of [<SUP>11</SUP>C]acetate using an in-house-developed module under different conditions has been reported for routine production. [<SUP>11</SUP>C]CO<SUB>2</SUB> was produced in a 16.4 MeV PETtrace cyclotron, and methyl magnesium chloride was used for synthesis. For product purification, ion-exchange solid-phase extraction cartridges were used, connected in series. High-performance liquid chromatography and gas chromatography were used to measure radiochemical and chemical purity. The Limulus amebocyte lysate test and the fluid thioglycollate medium test were performed for quality control of [<SUP>11</SUP>C]acetate. The total reaction time of [<SUP>11</SUP>C]acetate was within 15 min, and the overall decay-corrected radiochemical yield was 84.33±8.85%. Radiochemical purity was greater than 98% when evaluated on an analytical high-performance liquid chromatography system. No endotoxins or anaerobic bacteria were seen on quality control checks. Optimized production of [<SUP>11</SUP>C]acetate was achieved by the in-house module. Radiochemical and biological properties of the [<SUP>11</SUP>C]acetate produced were appropriate for clinical PET study.</P></▼2>
The relationship between maternal obesity in pre-pregnancy and preterm birth in Korean women
( Ayoung Song ),( Sung-eun Kim ),( Jae-young Sim ),( Eun-jin No ),( Ho Yeon Kim ),( Geum Joon Cho ),( Ki Hoon Ahn ),( Soon-cheol Hong ),( Hai-joong Kim ),( Min-jeong Oh ) 대한산부인과학회 2020 대한산부인과학회 학술대회 Vol.106 No.-
Objective: The prevalence of obesity and preterm birth steadily increased in Korea and obesity in early pregnancy has been known to be associated with maternal and perinatal complications. The aim of this study was to evaluate the effect of maternal pre-pregnancy obesity on the risk of preterm birth in Korean women. Methods: Primiparas who delivered a singleton between January 1, 2007 and December 31, 2015 and underwent a National Health Screening Examination within 1 year of pregnancy were eligible. The data of preterm birth was obtained by merging the data of the National Health Screening Program for Infants and Children database. Maternal obesity was defined as BMI ≥25kg/m2. Results: Among 237,062 women who delivered during the study period, 16,249 (6.85 %) women were obese. In the multivariable analysis, Women with obesity had an increased risk of preterm birth (<37 weeks of gestation) (OR, 1.14; 95% CI, 1.04, 1.23) compared with those without obesity. Women with obesity also had an increased risk of early preterm birth (<34 weeks of gestation) (OR, 1.44; 95% CI, 1.24, 1.69). Conclusion: Our study sustained actual relations between obesity in pre-pregnancy and the risk of preterm birth in Korea. Public health plan regarding obesity in prenatal counseling is needed to attend to optimal body weight gain before conception to mitigate the risk of poor perinatal outcomes.
Pyo, Ayoung,Yun, Misun,Kim, Hyeon Sik,Kim, Tae-Yoon,Lee, Joong-jae,Kim, Jung Young,Lee, Sunwoo,Kwon, Seong Young,Bom, Hee-Seung,Kim, Hak-Sung,Kim, Dong-Yeon,Min, Jung-Joon Society of Nuclear Medicine 2018 The Journal of nuclear medicine Vol.59 No.2
<P>The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 <SUP>64</SUP>Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. <B>Methods:</B> Repebodies were synthesized with the chelators 2-(<I>p</I>-isothiocyanatobenzyl)-1,4,7-triazacyclononane-<I>N,N′,N,″-</I>triacetic acid trihydrochloride ([<I>p</I>-SCN-Bn]-NOTA), 2,2′,2″-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA-<I>N</I>-hydroxysuccinimide ester), or 1-(<I>p</I>-isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([<I>p</I>-SCN-Bn]-DTPA) in 1.0 M NaHCO<SUB>3</SUB> buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with <SUP>64</SUP>Cu in 0.1 M NH<SUB>4</SUB>OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non–small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor–bearing mice. <B>Results:</B> Radiochemical yields of the <SUP>64</SUP>Cu-labeled repebodies were approximately 70%–80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor–bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). <B>Conclusion:</B> The 3 <SUP>64</SUP>Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.</P>