• Title/Summary/Keyword: $[^{11}C]$Choline

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A Study on the Synthesis and Its Biodistribution of C-11 and F-18 Labelled Choline (C-11 및 F-18 표지 콜린의 합성과 체내동태에 관한 연구)

  • Yang, Seung-Dae;Kim, Sang-Wook;Suh, Yong-Sup;Chun, Kwon-Soo;Ahn, Soon-Hyuk;Hur, Min-Goo;Lim, Sang-Moo;Hong, Sung-Woon;Yu, Kook-Hyun
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.3
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    • pp.185-191
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    • 2001
  • Objectives: Recently, $[methyl-^{11}C]-({\beta}$-Hydroxyethyl)trimethylammonium ($[^{11}C]$choline) Has been discovered to be a very effective tracer in imaging various human tumors using positron omission tomography. Because of the short half-life of C-11, it is very difficult to use in a routine imaging procedure and needs a frequent synthesis of $[^{11}C]$choline. This can be supplemented by the substitution of $[^{11}C]$choline with $[methyl-^{18}F]$fluorocholine. Here, we would like to report ceil uptake and biodistribution of $[^{11}C]$choline and $[^{18}F]$fluorocholine as a basic study. Methods: $[^{11}C]$Choline was prepared by the treatment of $[^{11}C]CH_3I$ with N,N-dimethylaminoethanol and $[^{18}F]$fluorocholine was synthesized from reaction of $CH_2Br[^{18}F]F$ with N,N-dimethylaminoethanol. The radiochemical purity was checked by high performance liquid chromatography (HPLC). The blodistribution of $[^{11}C]$choline and $[^{18}F]$fluorocholine was determined in balb/c mouse at 5 min, 20 min, 40 min and 80 min. The cell uptake was measured using glioma (9L) and colon adenocarcinoma (SW620). Results: The radiochemical purity was more than 98% after purification. In the liver, uptake did not change over time; the uptake was 20%ID/g for $[^{11}C]$choline and 13%ID/g for $[^{18}F]$fluorocholine. In the kidney, radioactivity decreased over time; the uptake was 15%ID/g for $[^{11}C]$choline and 20%ID/g for $[^{18}F]$fluorocholine, 80 min post-injection. The cell uptake of $[^{11}C]$choline was 4.93% for glioma (9L) and 18.69% for colon adenocarcinoma (SW620). For $[^{18}F]$fluorocholine, 1.77% for glioma (9L) and 2.77% for colon adenocarcinoma (SW620). Conclusion: $[^{11}C]$Choline and $[^{18}F]$fluorocholine showed a different cell uptake tendency, depending on cancer cell line.

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Diagnosis of Hepatocellular Carcinoma Using C-11 Choline PET/CT: Comparison with F-18 FDG, Contrast-Enhanced MRI and MDCT

  • Chotipanich, Chanisa;Kunawudhi, Anchisa;Promteangtrong, Chetsadaporn;Tungsuppawattanakit, Puntira;Sricharunrat, Thaniya;Wongsa, Paramest
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3569-3573
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    • 2016
  • Purpose: The aim of this study was to compare C-11 choline and F-18 FDG PET/CT, gadoxetic-enhanced 3-T MRI and contrast-enhanced CT for diagnosis of hepatocellular carcinoma (HCC). Materials and Methods: Twelve chronic hepatitis B patients suspected of having HCC by abdominal ultrasonography received all diagnostic modalities performed within a one-week timeslot. PET/CT results were analyzed visually by two independent nuclear medicine physicians and quantitatively by tumor to background ratio (T/B). Nine patients then had histopathological confirmation. Results: Six patients had well differentiated HCC, while two and one patient(s) were noted with moderately and poorly differentiated HCC, respectively. All were detected by both CT and MRI with an average tumor size of $5.7{\pm}3.8cm$. Five patients had positive C-11 choline and F-18 FDG uptake. Of the remaining four patients, three with well differentiated HCC showed negative F-FDG uptake (one of which showed negative results by both tracers) and one patient with moderately differentiated HCC demonstrated no C-11 choline uptake despite intense F-18 FDG avidity. The overall HCC detection rates with C-11 choline and F-18 FDG were 78% and 67%, respectively, while the sensitivity of F-18 FDG for non-well differentiated HCC was 100%, compared with 83% of C-11 choline. The average T/B of C-11 choline in well-differentiated HCC patients was higher than in moderately and poorly differentiated cases (p=0.5) and vice versa with statistical significance for T/B of F-18 FDG (p = 0.02). Conclusions: Our results suggested better detection rate in C-11 choline for well differentiated HCC than F-18 FDG PET. However, the overall detection rate of PET/CT with both tracers could not compare with contrast-enhanced CT and MRI.

FUNGAL EXTRACELLULAR POLYSACCHARIDES INVOLVED IN RECYCLING OF METABOLITES AND OSMOTOLERANCE OF PENICILLIUM FELLUTANUM : APPLICATION OF $^{13}$ C-NMR SPECTROSCOPY FOR THE STUDY ON FUNGAL PHYSIOLOGY AND METABOLISM

  • Park, Yong-Il;Gander, John.-E.
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 2000.04a
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    • pp.208-213
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    • 2000
  • Penicillium fellutanum produces a phosphorylated, choline-containing extracellular peptido-polysaccharide, peptidophosphogalactomannan (pPxGM) (8). The $\^$13/C-methyl labeled pPxGM ([methyl-$\^$13/C]pPxGM) was prepared from the cultures supplemented with L-[methyl-$\^$13/C]methionine or [2-$\^$13/C]glycine and was used as a probe to monitor the fate of phosphocholine in this polymer. Addition of purified [methyl-$\^$l3/C]pPxGM to growing cultures in low phosphate medium resulted in the disappearance of [methyl-$\^$13/C]phosphocholine and -N,N'-dimethyl-phosphoethanolamine from the added [methyl-$\^$13/C]pPxGM. Two $\^$l3/C-methyl-enriched cytoplasmic solutes, choline-O-sulfate and glycine betaine, were found in mycelial extracts, suggesting that phosphocholine-containing extracellular pPxGM of P.fellutanum is a precursor of intracellular choline-O-sulfate and glycine betaine and thus of phosphatydilcholine (l0). $\^$13/C-Methyl-labeled cells grown in 3 M NaCl-containing medium showed 2.6- and 22-fold more accumulation of $\^$13/C-methyl labeled choline-O-sulfate and glycine betaine, respectively, originated from the extracellular [$\^$13/C-methyl]pPxGM than those grown without added NaCl. The results suggest that, in addition to glycerol and erythritol, glycine betaine and choline-O-sulfate and thus choline are also osmoprotectants and hence that pPxGM is involved in osmotolerance of this fungus (11). Taken collectively, the $\^$l3/C- and $\^$31/P-NMR analyses of cytosolic solute pools and structural modulation of extracellular pPxGM corresponding to environmental stimuli in P. fellutanum, provided evidence that pPxGM is involved in cellular choline metabolism, osmotolerance, and recycling of metabolites.

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Synthesis of [18F]Fluorocholine Analogues as a Potential Imaging Agent for PET Studies

  • Yu, Kook-Hyun;Park, Jeong-Hoon;Yang, Seung-Dae
    • Bulletin of the Korean Chemical Society
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    • v.25 no.4
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    • pp.506-510
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    • 2004
  • There have been intensive studies concerning $[^{11}F]$choline ($[^{11}F]$methyldimethyl( ${\beta}$ -hydroxyethyl) ammonium) (1) which is known as a very effective tracer in imaging various human tumors localized in brain, lung, esophagus, rectum, prostate and urinary bladder using Positron Emission Tomography (PET) and there is increasing interest in $^{18}F$ labelled choline (2) and proved to be useful to visualize prostate cancer. We have prepared six $^{18}F$ labelled alkyl choline derivatives (3a-3c, 4a-4c) from ditosylated and dibrominated alkanes in moderate yields. The six alkyl tosylate or bromate ammonium salts have been synthesized as precursors. Radiofluorination was achieved by the treatment of precursors with $^{18}F$ - in the presence of Kryptofix-2.2.2.. The labeling yields varied ranging from 7 to 25%.

Nuclear Imaging of Cellular Proliferation (핵의학적 세포증식 영상)

  • Yeo, Jeong-Seok
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.2
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    • pp.198-204
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    • 2004
  • Tumor cell proliferation is considered to be a useful prognostic indicator of tumor aggressiveness and tumor response to therapy but in vitro measurement of individual proliferation is complex and tedious work. PET imaging provides a noninvasive approach to measure tumor growth rate in situ. Early approaches have used $^{18}F$-FDG or methionine to monitor proliferation status. These 2 tracers detect changes in glucose and amino acid metabolism, respectively, and therefore provide only an indirect measure of proliferation status. More recent studies have focused on DNA synthesis itself as a marker of cell proliferation. Cell lines and tissues with a high proliferation rate require high rates of DNA synthesis. $[^{11}C]Thymidine$ was the first radiotracer for noninvasive imaging of tumor proliferation. The short half-life of $^{11}C$ and rapid metabolism of $[^{11}C]Thymidine$ in vivo make the radiotracer less suitable for routing use. Halogenated thymidine analogs such as 5-iodo-2-deoxyuridine (IUdR) can be successfully used as cell proliferation markers for in vitro studies because these compounds are rapidly incorporated into newly synthesized DNA. IUdR has been evaluated as a potential in vivo tracer in nuclear medicing but the image qualify and the calculation of proliferation rates are impaired by its rapid in vivo degradation. Hence, the thymidine analog $3'-deoxy-3'-^{18}F-fluorothymidine$ (FLT) was recently introduced as a stable proliferation marker with a suitable nuclide half-life and stable in vivo. $[^{18}F]FLT$ is phosphorylated to 3-fluorothymidine monophosphate by thymidine kinase 1 and reflects thymidine kinase 1 activity in proliferating cell. $[^{18}F]FLT$ PET is feasible in clincal use and well correlates with cellular proliferation. Choline is a precursor for the biosynthesis of phospholipids (in particular, phosphatidylcholine), which is the essential component of all eukaryotic cell membranes and $[^{11}C]choline$, which is a new marker for cellular proliferation.

Effects of DNA Synthesis Inhibitors on the Expression of c-myc and the Stimulation of Choline Acetyltransferase Activity in Human Neuroblastoma Cell Line, IMR-32 (DNA합성 억제제가 IMR-32 세포의 c-myc 발현 및 Choline Acetyltransferase 활성도에 미치는 영향)

  • 이정은;조경혜
    • Biomedical Science Letters
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    • v.3 no.1
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    • pp.11-20
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    • 1997
  • A regulation of differentiation in human neuroblastoma cells remains poorly understood, although it is of great importance in the clinical therapy of neuroblastoma. This study was aimed to elucidate effects of DNA synthesis inhibitors on the differentiation of neuroblastoma cells on the basis of morphological, biochemical and molecular respects. Three DNA synthesis inhibitors, sodium butyrate, hydroxyurea, cytosine arabinoside were used to explore their effects on the cellular morphology, the expression of c-myc and the elevation of choline acetyltransferase activity. They led to the extension or neurite-like processes reflecting differentiation or IMR-32 cells. In addition, the treatment of three DNA synthesis inhibitors resulted in the remarkable increases in the expression of c-myc as well as the stimulation of choline acetyltransferase activity which is involved in the synthesis of acetylcholine in the differentiated cholinergic neurons. Taken together, these results indicate that DNA synthesis inhibitors play an important role in the induction of cellular differentiation in IMR-32 cells. Furthermore these DNA synthesis inhibitors seem to be future useful to give an important clue (for the treatment of neuroblastoma).

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Extraction and Composition of Bound Lipids in Naked Barley (쌀보리 결합지질의 추출과 그 조성에 관한 연구)

  • Kim, Hae-Gyoung;Kim, Bok-Nam;Choi, Hong-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.18 no.1
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    • pp.109-114
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    • 1989
  • Bound lipids(BL) of naked barley(Hordeum vulgare L.) were extracted by different methods and the composition of BL was determined by the procedures of column chromatography, thin layer chromatography and gas chromatography. For the extraction, after free lipids were removed from barley flour by petroleum ether(PE) extraction and then BL were extracted from PE treated flour by the solvent systems of water-saturated butanol(WSB) at $25^{\circ}C$(WSB-LT) and at $95^{\circ}C$ (WSB-HT). BL were extracted by WSB-HT with higher extraction yield as 1.5% as dry basis of flour. The contents of neutral lipids(NL), glycolipids(GL) and phospholipid(PL) in BL were $20.7{\sim}35.5%$, $28.7{\sim}32.4%$, $32.1{\sim}50.6%$, respectively with particularly higher content of PL in WSB-HT as 50.6%. Digalactosyl-diglycerides $(40.2{\sim}44.8%)$, monogalactosyl-diglycerides $(20.3{\sim}31.1%)$, sterly glycerides$(11.2{\sim}15.2%)$ and cereb rosides$(11.6{\sim}12.9%)$ were observed in GL. Of the PL in BL, lysophosphatidyl choline, phosphatidyl choline and phosphatidyl serine, and phosphatidyl ethanolamine were the major components. The predominent fatty acids of NL, GL and PL were linoleic and palmitic acids, however, no significant difference was observed in the composition of fatty acids between two extraction methods.

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Studies on Lipids in Fresh-Water Fishe 2. Distribution of Lipid Components in Various Tissues of Snake Head, Channa argus (담수어의 지질에 관한 연구 2. 가물치(Channa argus)의 부위별 지질성분의 분포)

  • RO Jae-Il;CHOI Jin-Ho;PYEUN Jae-Hyeung;JANG Jin-Gyu
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.17 no.5
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    • pp.405-413
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    • 1984
  • As the previous paper of studios on lipids in fresh-water fishes, the present study was designed and analyzed to investigate the distribution of lipid components in various tissues of snake head, Channa argus. The free lipid was consisted of neutral lipid ($66.6{\sim}72.4\%$), phospholipid($17.9{\sim}20.4\%$) and glycolipid ($5.7{\sim}12.2\%$), while the bound lipid was consisted of phospholipid($28.6{\sim}50.6\%$), neutral lipid($13.2{\sim}36.1\%$) and glycolipid($3.8{\sim}22.8\%$). The neutral lipid was mainly consisted of triglyceride($62.00{\sim}90.20\%$) in free lipid, and esterified sterol & hydrocarbon($51.30{\sim}72.70\%$) in bound lipid. The phospholipid was mainly consisted of phosphatidyl ethanolamine($28.96{\sim}42.75\%$) and phosphatidyl choline ($27.85{\sim}41.06\%$) in free lipid, and phosphatidyl choline($47.18{\sim}52.45\%$) and phosphatidyl ethanolamine ($17.88{\sim}26.67\%$) in bound lipid. The major fatty acids of polar lipid in free and bound lipids were $C_{16:0}(21.03\%,\;22.62\%),\;C_{16:1}(8.70\%,\;30.1\%),\;C_{18:1}(20.62\%,\;12.11\%),\;C_{22:5}(3.21\%,\;6.50\%)\;and\;C_{22:6}(7.56\%,\;16.02\%)$, and these of neutral lipid in free and bound lipids were $C_{16:0}(18.98\%,\;19.12\%),\;C_{16:1}(9.04\%,\;13.49\%),\;C_{18:1}(22.94\%,\;11.61\%)\;and\;C_{22:5}(3.00\%,\;10.05\%)$, respectively. The unsaturation(TUFA/TSFA) of bound lipid was 3.99, and 2.5 times higher than 1.43 of free lipid. The contents of total essential fatty acid in free lipid were ranged $7.99\%\;to\;14.69\%$, and slightly higher than $6.57\%\;to\;8.25\%$ of bound lipid. In both polar and nonpolar lipids, w3 highly unsaturated fatty acid(w3-HUFA) contents of bound lipid were ranged $22.57\%\;to\;31.83\%$, and $2{\sim}3$ times higher than $7.88\%\;to\;14.03\%$ of free lipid. There were significant difference between the lipid and its fatty acid composition in free and bound lipids and/or in various tissues.

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Characteristics of $G_{418}$-sensitive mitochondrial ATPase/ATP synthase from pleurotus florida (사철느타리버섯 중 $G_{418}$-sensitive 미토콘드리아성 ATPase/ATP synthase의 특성)

  • Kim, Jae-Woong;Kim, Dong-Hee;Lee, Jung-Bock;Lee, Sur-Koo;Min, Tae-Jin
    • Analytical Science and Technology
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    • v.5 no.4
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    • pp.477-484
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    • 1992
  • The mitochondrion was purified at 44% sucrose layer from pleurotus florida by using ultracentrifuge and sucrose density gradient method. Optimum pH and temperature of ATPase and ATP synthase were pH 7.4, $60^{\circ}C$ and pH 7.5, $57^{\circ}C$ respectively, also their Km values were determined as 11.6mM and 8.4mM. ATPase was activated at 5~6mM ATP substrate concentration, then ATP synthase was 5~10mM range ADP. ATPase/ATP synthase were $Mg^{2+}$-dependent enzyme, partially inhibited by their substrate, and then showed an none competitive inhibition pattern by $G_{418}$. Amino acid composition of ATPase/ATP synthase was as follows, hydrophobic amino acid residue was 50.5%, small residue, 56.1%, hydrogen bonding residue, 43.7% and helix breaking residue, 55.2%. Phosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl glycerol were contained but not phosphatidyl inositol and phosphatidyl serine. Palmitate(51.31%), stearate(18.32%) and unsaturated fatty acids($C_{18:1}$, $C_{18:2}$ and $C_{16:1}$) were predominated.

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The Effect of Acori Graminei Rhizoma Pharmacopuncture at GV20 on Dementia in a Focal Cerebral Ischemia Mice Model

  • Jang, Yeo jin;Kwak, Min Kyung;Jeong, Sang Jun;Kim, Hye Hwa;Kim, Tae Gwang;Kim, Jae Hong
    • Journal of Acupuncture Research
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    • v.34 no.3
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    • pp.1-11
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    • 2017
  • Objectives : The purpose of this study was to examine the effects of Acori Graminie Rhizoma Pharmacopuncture (PA-AG) at GV20 on cerebral ischemia-induced dementia in Mice. Methods : Mice were divided into the five following groups: normal, control, acupuncture, PA-AG (17 mg/kg), and PA-AG (34 mg/kg). All groups, except the normal group, had cerebral ischemia induced by occlusion of middle cerebral artery. The control group was not treated. The acupuncture, PA-AG (17 mg/kg), and PA-GA (34 mg/kg) groups were treated every other day with a total of 6 treatments. The effect of treatment was observed by Bax, Bcl-2, Bax/Bcl-2 ratio, cytochrome c, cresyl violet, and choline acetyltransferase staining. Results : In the PA-AG (34 mg/kg) group, the intensity of Bax was decreased and the intensity of Bcl-2 was increased. The Bax/Bcl-2 ratio also decreased in the PA-AG (34 mg/kg) group. The intensity of cytochrome c protein stain was decreased in the PA-AG (17 mg/kg) group. The density of neurons stained by cresyl violet and choline acetyltransferase (ChAT) was increased in the AT, PA-AG (17 mg/kg), and PA-AG (34 mg/kg) groups when compared with that of the control group. Conclusion : PA-AG at GV20 was effective on cerebral ischemia-induced dementia in mice.