Sample records for pyruvaldehyde

  1. Brønsted acid ionic liquid catalyzed formation of pyruvaldehyde dimethylacetal from triose sugars

    DEFF Research Database (Denmark)

    Shunmugavel, Saravanamurugan; Riisager, Anders


    A series of sulfonic acid functionalized ionic liquids (SO3H-ILs) have been synthesized, characterized and investigated as catalysts for the conversion of the triose sugars, 1,3-dihydroxyacetone (DHA) and glyceraldehyde (GLA), to pyruvaldehyde dimethylacetal (PADA) in methanol. Depending...

  2. Structural characterization of a metal-based perfusion tracer: copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone). (United States)

    John, E; Fanwick, P E; McKenzie, A T; Stowell, J G; Green, M A


    Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone), Cu(PTSM), has been obtained as a dark red crystalline solid from EtOH-DMSO solvent mixture and structurally characterized by x-ray crystallography. The molecule possesses the expected pseudo-square planar N2S2 metal coordination sphere; however, the copper center also interacts through its axial coordination site with the sulfur atom of an adjacent Cu(PTSM) molecule in the crystal lattice. The structure of this compound is compared with the structures of other metal complexes that have been proposed in the nuclear medicine literature as perfusion tracers.

  3. Biodistribution study of [61Cu] pyruvaldehyde-bis (N-4-methylthiosemicarbazone) in normal rats as a PET tracer

    Institute of Scientific and Technical Information of China (English)



    [61Cu]-labeled pyruvaldehyde-bis (N-4-methylthiosemicarbazone) (61Cu-PTSM), a promising agent made for imaging blood perfusion, was produced via the natZn(p,x)61Cu nuclear reaction in a 30 MeV cyclotron, and separated by a two-step column chromatography method developed in our laboratory using a cation and an anion exchange resin. After 150μA irradiation for 76 min, about 6.006 Ci of 61Cu2+ was obtained with a radiochemical separation yield of 95% and a radionuclidic purity of 99%. 61Cu-PTSM was prepared using an optimized method with in-house synthesized PTSM ligand for radiolabeling following quality control procedures using RTLC and HPLC. The tracer is mostly incorporated in heart, kidneys and brain compared to free copper cation as a control. These are in agreement with former reports. In conclusion, [61Cu]-PTSM was prepared at the radiopharmaceutical scales with high quality and is a potential PET tracer in the perfusion study of the heart, kidney, brain and tumors.

  4. Mitochondria-selective reduction of [sup 62]Cu-pyruvaldehyde bis(N[sup 4]-methylthiosemicarbazone)([sup 62]Cu-PTSM) in the murine brain; A novel radiopharmaceutical for brain positron emission tomography (PET) imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fujibayashi, Yasuhisa; Wada, Kouichi; Taniuchi, Hideyuki; Yonekura, Yoshiharu; Konishi, Junji; Yokoyama, Akira (Kyoto Univ. (Japan). Faculty of Medicine)


    The retention mechanism of [sup 62]Cu-pyruvaldehyde bis(N[sup 4]-methylthiosemicarbazone)([sup 62]Cu-PTSM) in the murine brain was evaluated. For this purpose, stable Cu-PTSM was subjected to electron spin resonance spectrometry (ESR) and high performance liquid chromatography (HPLC) analysis to determine the valence state, coordination structure and tissue metabolism. In murine brain homogenate, ESR and HPLC analysis indicated the reduction and cleavage of Cu(II)-PTSM to Cu(I). This virtually irreversible reduction was specifically initiated by the mitochondrial enzymatic system in the murine brain. (author).

  5. Cu-pyruvaldehyde-bis(N{sup 4}-methylthiosemicarbazone)(Cu-PTSM), a metal complex with selective NADH-dependent reduction by complex I in brain mitochondria. A potential radiopharmaceutical for mitochondria-functional imaging with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Taniuchi, Hideyuki; Fujibayashi, Yasuhisa; Yokoyama, Akira [Kyoto Univ. (Japan). Faculty of Pharmaceutical Science; Okazawa, Hidehiko; Yonekura, Yoshiharu; Konishi, Junji


    The reductive retention mechanism of copper(II)-Pyruvaldehyde-bis (N{sup 4}-methylthiosemicarbazone) (Cu-PTSM), a generator-produced positron-emitting {sup 62}Cu-labeled radiopharmaceutical, was studied with non-radioactive and radioactive copper. Changes in the chemical form of Cu-PTSM were detected by electron spin resonance spectrometry (ESR) with cold copper. The effects of electron transport chain inhibitors on the reduction of Cu-PTSM were also examined. Rotenone and antimycin A activated the reduction of Cu-PTSM in the brain mitochondria by 1.6 and 1.4-fold, respectively, compared with untreated controls, while thenoyltrifluoroacetone (TTFA) had no effect on the reduction. These results were confirmed with radioactive copper. Furthermore, this reduction of Cu-PTSM was dependent on the protein concentration of mouse brain submitochondrial particle (SMP) with 1 mM NADH2.S%, 8mg-protein/ml: 69.0{+-}5.5%, each value was % of reduced Cu. Similarly, this reduction depended on NADH concentration at a fixed concentration of SMP (8mg-protein/ml). These results indicated that the electron transport chain, especially complex I, participate in the reduction mitochondria, and this suggested that Cu-PTSM has the potential to act as a functional imaging agent for diagnosis of the electron transport chain. (author).

  6. Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde-bis (N-4-methylthiosemicarbazone), Cu-PTSM. (United States)

    Kostyniak, P J; Nakeeb, S M; Schopp, E M; Maccubbin, A E; John, E K; Green, M A; Kung, H F


    Cu-PTSM is a potential imaging agent for the heart and brain when labeled with either 64Cu or 62Cu. Unlabeled Cu-PTSM was evaluated for its acute toxicity and mutagenicity. Cu-PTSM had an i.v. LD50 of 26 mg kg-1 in the rat and 2 mg kg-1 in the rabbit. At necropsy, rats exhibited severely hemorrhagic lungs, histological findings of acute pulmonary congestion, hemorrhage and edema, and mild congestion in kidney, liver and brain. The rabbit displayed marked polymorphonuclear infiltration in alveoli, peribronchial and periarterial areas with marked macrophage hyperplasia, congestion and mild hemorrhage into alveolar spaces. No effects were found in kidney, liver, testes or brain. Administration of 2.16 micrograms kg-1 day-1 for 5 days per week for 2 weeks resulted in no changes in histopathology, hematology or clinical chemistry parameters. This daily dose is at least 300 times the diagnostic dose intended for use in man. Cu-PTSM was not mutagenic when tested in the absence of S9 supernatant, but elicited a weakly mutagenic response in the presence of S9. Since acute effects in the lung occur at doses approaching 300,000 times the diagnostic dose, it is highly unlikely that the clinical use of Cu-PTSM would result in any acute adverse effects.

  7. Cells producing their own nemesis: understanding methylglyoxal metabolism. (United States)

    Chakraborty, Sangeeta; Karmakar, Kapudeep; Chakravortty, Dipshikha


    Methylglyoxal, which is technically known as 2-oxopropanal or pyruvaldehyde, shows typical reactions of carbonyl compounds as it has both an aldehyde and a ketone functional group. It is an extremely cytotoxic physiological metabolite, which is generated by both enzymatic and nonenzymatic reactions. The deleterious nature of the compound is due to its ability to glycate and crosslink macromolecules like protein and DNA, respectively. However, despite having toxic effects on cellular processes, methylglyoxal retains its efficacy as an anticancer drug. Indeed, methylglyoxal is one of the well-known anticancer therapeutic agents used in the treatment. Several studies on methylglyoxal biology revolve around the manifestations of its inhibitory effects and toxicity in microbial growth and diabetic complications, respectively. Here, we have revisited the chronology of methylglyoxal research with emphasis on metabolism of methylglyoxal and implications of methylglyoxal production or detoxification on bacterial pathogenesis and disease progression.

  8. Stable reagent for the detection of antibody to the specific fraction I antigen of Yersinia pestis. (United States)

    Rust, J H; Berman, S; Habig, W H; Marshall, J D; Cavanaugh, D C


    A stable hemagglutinating antigen for detection of fraction I (FR-I) antibody of Yersinia pestis (Pasteurella pestis) is described. The antigen was prepared by sensitizing tanned, pyruvaldehyde-treated sheep erythrocytes (PAT SRBC) with FR-I antigen. Preliminary standardization by titration of each lot of FR-I was required to minimize the effect of molecular heterogeneity of specific FR-I antigen and to eliminate nonspecific reactions caused by the presence of a minor antigenic contaminant. In tests with sera from rabbits, dogs, and humans, FR-I PAT SRBC were as reactive as the previously employed standard antigen, FR-I-sensitized tanned erythrocytes. Fluid suspensions of FR-I PAT SRBC stored at 4 C for 3 months, or lyophilized preparations stored at ambient temperature for 6 months, showed no loss in antigenic activity.

  9. Stable Reagent for the Detection of Antibody to the Specific Fraction I Antigen of Yersinia pestis1 (United States)

    Rust, James H.; Berman, Sanford; Habig, William H.; Marshall, John D.; Cavanaugh, Dan C.


    A stable hemagglutinating antigen for detection of fraction I (FR-I) antibody of Yersinia pestis (Pasteurella pestis) is described. The antigen was prepared by sensitizing tanned, pyruvaldehyde-treated sheep erythrocytes (PAT SRBC) with FR-I antigen. Preliminary standardization by titration of each lot of FR-I was required to minimize the effect of molecular heterogeneity of specific FR-I antigen and to eliminate nonspecific reactions caused by the presence of a minor antigenic contaminant. In tests with sera from rabbits, dogs, and humans, FR-I PAT SRBC were as reactive as the previously employed standard antigen, FR-I-sensitized tanned erythrocytes. Fluid suspensions of FR-I PAT SRBC stored at 4 C for 3 months, or lyophilized preparations stored at ambient temperature for 6 months, showed no loss in antigenic activity. PMID:5062977

  10. Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM. (United States)

    Mathias, C J; Welch, M J; Raichle, M E; Mintun, M A; Lich, L L; McGuire, A H; Zinn, K R; John, E K; Green, M A


    Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.6 days) and 64Cu (t1/2 = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM2 continued to clear. Cu-PTSM and Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of [64Cu]-Cu-PTSM. For comparison with the 64Cu brain image, a CBF (15O-labeled water) image (40 sec) was first obtained. Qualitatively, the H2(15)O and [64Cu]-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H2(15)O and 2.67 for Cu-PTSM. No redistribution of 64Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H2(15)O. This data suggests that [62Cu]-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.

  11. Degradation of tert-butyl formate and its intermediates by an ozone/UV process. (United States)

    Garoma, Temesgen; Gurol, Mirat D; Thotakura, Lalitha; Osibodu, Olufisayo


    In this paper, the oxidation of tert-butyl formate (TBF) in aqueous solution by an ozone/UV process was described. The oxidation process was investigated experimentally in a semibatch reactor. The results of the study indicated that the ozone/UV process was very effective in oxidizing TBF. tert-Butyl alcohol (TBA), hydroxy-iso-butyraldehyde (HiBA), acetone, formaldehyde, and formic acid were identified as major primary intermediates during the oxidation of TBF. About 90% organic carbon balance was obtained indicating that most reaction intermediates have been identified and quantified. Some of the primary intermediates were also oxidized in the ozone/UV system. Accordingly, HiBA, acetone, formaldehyde, and formic acid were the primary intermediates of TBA oxidation. The oxidation of acetone in the ozone/UV system generated formaldehyde, pyruvaldehyde, acetic acid, formic acid as primary intermediates. It was also observed that the reaction intermediates formed during the oxidation of TBF react well in the ozone/UV system and complete mineralization could be achieved by the process.

  12. Cu(II) bis(thiosemicarbazone) radiopharmaceutical binding to serum albumin: further definition of species dependence and associated substituent effects

    Energy Technology Data Exchange (ETDEWEB)

    Basken, Nathan E. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States); Green, Mark A. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail:


    Introduction: The pyruvaldehyde bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and diacetyl bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-ATSM) radiopharmaceuticals exhibit strong, species-dependent binding to the IIA site of human serum albumin (HSA), while the related ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) radiopharmaceutical appears to exhibit only nonspecific binding to HSA and animal serum albumins. Methods: To further probe the structural basis for the species dependence of this albumin binding interaction, we examined protein binding of these three radiopharmaceuticals in solutions of albumin and/or serum from a broader array of mammalian species (rat, sheep, donkey, rabbit, cow, pig, dog, baboon, mouse, cat and elephant). We also evaluated the albumin binding of several copper(II) bis(thiosemicarbazone) chelates offering more diverse substitution of the ligand backbone. Results: Cu-PTSM and Cu-ATSM exhibit a strong interaction with HSA that is not apparent with the albumins of other species, while the binding of Cu-ETS to albumin is much less species dependent. The strong interaction of Cu-PTSM with HSA does not appear to simply correlate with variation, relative to the animal albumins, of a single amino acid lining HSA's IIA site. Those agents that selectively interact with HSA share the common feature of only methyl or hydrogen substitution at the carbon atoms of the diimine fragment of the ligand backbone. Conclusions: The interspecies variations in albumin binding of Cu-PTSM and Cu-ATSM are not simply explained by unique amino acid substitutions in the IIA binding pocket of the serum albumins. However, the specific affinity for this region of HSA is disrupted when substituents bulkier than a methyl group appear on the imine carbons of the copper bis(thiosemicarbazone) chelate.

  13. A comparison of PET imaging characteristics of various copper radioisotopes

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Heather Ann [North Western Medical Physics, Christie Hospital NHS Trust, Manchester (United Kingdom); University of Manchester Institute of Science and Technology, Department of Instrumentation and Analytical Science, Manchester (United Kingdom); Robinson, Simon; Julyan, Peter; Hastings, David [North Western Medical Physics, Christie Hospital NHS Trust, Manchester (United Kingdom); Zweit, Jamal [University of Manchester Institute of Science and Technology, Department of Instrumentation and Analytical Science, Manchester (United Kingdom); Paterson Institute for Cancer Research, Radiochemical Targeting and Imaging, Manchester (United Kingdom)


    PET radiotracers which incorporate longer-lived radionuclides enable biological processes to be studied over many hours, at centres remote from a cyclotron. This paper examines the radioisotope characteristics, imaging performance, radiation dosimetry and production modes of the four copper radioisotopes, {sup 60}Cu,{sup 61}Cu,{sup 62}Cu and{sup 64}Cu, to assess their merits for different PET imaging applications. Spatial resolution, sensitivity, scatter fraction and noise-equivalent count rate (NEC) are predicted for{sup 60}Cu,{sup 61}Cu,{sup 62}Cu and{sup 64}Cu using a model incorporating radionuclide decay properties and scanner parameters for the GE Advance scanner. Dosimetry for{sup 60}Cu,{sup 61}Cu and{sup 64}Cu is performed using the MIRD model and published biodistribution data for copper(II) pyruvaldehyde bis(N{sup 4}-methyl)thiosemicarbazone (Cu-PTSM). {sup 60}Cu and{sup 62}Cu are characterised by shorter half-lives and higher sensitivity and NEC, making them more suitable for studying the faster kinetics of small molecules, such as Cu-PTSM.{sup 61}Cu and{sup 64}Cu have longer half-lives, enabling studies of the slower kinetics of cells and peptides and prolonged imaging to compensate for lower sensitivity, together with better spatial resolution, which partially compensates for loss of image contrast.{sup 61}Cu-PTSM and{sup 64}Cu-PTSM are associated with radiation doses similar to [{sup 18}F]-fluorodeoxyglucose, whilst the doses for{sup 60}Cu-PTSM and{sup 62}Cu-PTSM are lower and more comparable with H{sub 2}{sup 15}O. The physical and radiochemical characteristics of the four copper isotopes make each more suited to some imaging tasks than others. The results presented here assist in selecting the preferred radioisotope for a given imaging application, and illustrate a strategy which can be extended to the majority of novel PET tracers. (orig.)

  14. Structure-activity relationships for metal-labeled blood flow tracers: comparison of keto aldehyde bis(thiosemicarbazonato)copper(II) derivatives. (United States)

    John, E K; Green, M A


    Radiocopper-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II), Cu[PTSM], is under investigation as a radiopharmaceutical for evaluation of regional blood flow in the brain, heart, and kidneys because it affords relatively high levels of radioactivity in these organs upon intravenous injection, followed by prolonged tissue retention of the radiolabel. To probe and differentiate the physicochemical properties that are critical for blood-brain barrier (BBB) penetration and tissue retention in complexes of this type, 17 67Cu-labeled copper(II) bis(thiosemicarbazone) derivatives of Cu[PTSM] have been prepared and characterized, focusing on the bis(thiosemicarbazone), bis(N4-methylthiosemicarbazone), bis(N4-dimethylthiosemicarbazone), and bis(N4-ethylthiosemicarbazone) derivatives of several alkylglyoxals (R(1) = Me, Et, n-Pr, i-Pr, n-Bu, or Me(EtO)CH) and phenylglyoxal. The compounds studied varied in lipophilicity from log P = 0.75 to log P = 3.5 (where P is the octanol/water partition coefficient). In rat biodistribution studies the N4-methylthiosemicarbazone (R(1)TSM) and N4-dimethylthiosemicarbazone (R(1)TSM2) complexes always show comparable cerebral uptake at 1 min postinjection (iv) for any given R(1) group, while the thiosemicarbazone (R(1)TS) complex always penetrates the BBB less efficiently. Comparison of the various Cu[R(1)TS] derivatives shows that their brain uptake does tend to increase with increasing lipophilicity over the range 0.75 less than log P less than 2.4, although it never reaches that of the N4-alkylated derivatives. The Cu[R(1)TS] and Cu[R(1)TSM] complexes are found to exhibit prolonged cerebral retention of activity, consistent with their known susceptibility to reductive decomposition by intracellular sulfhydryl groups, while the more inert Cu[R(1)TSM2] complexes clear from the brain relatively rapidly. Tracer clearance kinetics in the heart and kidney are similar to those observed for the brain with each of the tracers

  15. Preparation of Radiopharmaceuticals Labeled with Metal Radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.


    The overall goal of this project was to develop methods for the production of metal-based radionuclides, to develop metal-based radiopharmaceuticals and in a limited number of cases, to translate these agents to the clinical situation. Initial work concentrated on the application of the radionuclides of Cu, Cu-60, Cu-61 and Cu-64, as well as application of Ga-68 radiopharmaceuticals. Initially Cu-64 was produced at the Missouri University Research Reactor and experiments carried out at Washington University. A limited number of studies were carried out utilizing Cu-62, a generator produced radionuclide produced by Mallinckrodt Inc. (now Covidien). In these studies, copper-62-labeled pyruvaldehyde Bis(N{sup 4}-methylthiosemicarbazonato)-copper(II) was studied as an agent for cerebral myocardial perfusion. A remote system for the production of this radiopharmaceutical was developed and a limited number of patient studies carried out with this agent. Various other copper radiopharmaceuticals were investigated, these included copper labeled blood imaging agents as well as Cu-64 labeled antibodies. Cu-64 labeled antibodies targeting colon cancer were translated to the human situation. Cu-64 was also used to label peptides (Cu-64 octriatide) and this is one of the first applications of a peptide radiolabeled with a positron emitting metal radionuclide. Investigations were then pursued on the preparation of the copper radionuclides on a small biomedical cyclotron. A system for the production of high specific activity Cu-64 was developed and initially the Cu-64 was utilized to study the hypoxic imaging agent Cu-64 ATSM. Utilizing the same target system, other positron emitting metal radionuclides were produced, these were Y-86 and Ga-66. Radiopharmaceuticals were labeled utilizing both of these radionuclides. Many studies were carried out in animal models on the uptake of Cu-ATSM in hypoxic tissue. The hypothesis is that Cu-ATSM retention in vivo is dependent upon the