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At least 19 recordsLinked to original sources
PubMed1998

Pre-clinical comparison of [DTPA0] octreotide, [DTPA0,Tyr3] octreotide and [DOTA0,Tyr3] octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy.

We have evaluated the potential usefulness of radiolabelled [DTPA0,Tyr3]octreotide and [DOTA0,Tyr3]octreotide as radiopharmaceuticals for somatostatin receptor-targeted scintigraphy and radiotherapy. In vitro somatostatin receptor binding and in vivo metabolism in rats of the compounds were investigated in comparison with [111In-DTPA0] octreotide. Comparing different peptide-chelator constructs, [DTPA0,Tyr3]octreotide and [DOTA0,Tyr3]octreotide were found to have a higher affinity than [DTPA0]octreotide for subtype 2 somatostatin receptors (sst2) in mouse AtT20 pituitary tumour cell membranes (all IC50 values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both 111In-labelled [DOTA0,Tyr3]octreotide and [DTPA0,Tyr3]octreotide in sst2-expressing tissues than after injection of [111In-DTPA0]octreotide, showing that substitution of Tyr for Phe at position 3 in octreotide results in an increased affinity for its receptor and in a higher target tissue uptake. Uptake of 111In-labelled [DTPA0]octreotide, [DTPA0,Tyr3]octreotide and [DOTA0,Tyr3]octreotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled octreotide/rat, indicating specific binding to sst2. Comparing different radionuclides, [90Y-DOTA0,Tyr3]octreotide had the highest uptake in sst2-positive organs, followed by the [111In-DOTA0,Tyr3]octreotide, whereas [DOTA0,125I-Try3]octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of 111In-labelled [DTPA0]octreotide, [DTPA0,Tyr3]octreotide and [DOTA0,Tyr3]octreotide was reduced over 50% by an i.v. injection of 400 mg/kg D-lysine, whereas radioactivity in blood, pancreas and adrenals was not affected.

Animals↗
PubMed1997

Enhancement of the molecular ion yield in plasma desorption mass spectrometry using explosive matrices.

The working hypothesis of this study was that the chemical energy of matrix material may be released, although only on a microscale, under MeV ion bombardment and may assist ejection of large intact bioorganic molecules. To test the hypothesis, the performance of several common explosives, as matrices in plasma desorption mass spectrometry, was compared to the standard matrix, nitrocellulose (NC), which is also a high explosive. Two explosives, RDX and HMX, were found to be new, effective matrices for peptides and proteins. While the performance of RDX was comparable with that of nitrocellulose, HMX gave a superior molecular ion yield and a higher average charge state of desorbed molecular ions compared with NC. Noth RDX and HMX have a similar chemical composition and structure, although the latter is a more powerful explosive. The measured total ion yield allows the conclusion that the increase in the amount of ejected material, due to the chemical energy release in high explosives under MeV ion bombardment, is limited, perhaps to a factor of 2 to 3. The fact that not all tested explosives gave molecular ions from peptides and proteins suggests that other factors, such as gas-phase chemistry, may play a significant role in molecular ion formation.

Animals↗
PubMedDate not supplied

Effects of the composition of bacteriological growth media on a chemiluminometric assay of beta-galactosidase in Escherichia coli.

The effects of the composition of bacteriological growth media on the light output in a chemiluminometric assay of beta-galactosidase in Escherichia coli using 1,2-dioxetane substrates has been studied. In this assay a basic conflict exists between conditions that promote optimal bacterial growth and those conducive to maximal chemiluminescence. Common medium ingredients such as yeast or beef extract, protein hydrolysates and lactose suppress light emission and/or lead to high backgrounds. Quenching of light emission is probably partly due to light absorption by medium ingredients such as oxgall, and partly to interference with the reaction triggering the chemiluminescent process. Elevated backgrounds are caused by the presence of high concentrations of protein hydrolysates, which interact with the alkali in the accelerator solution. Only two purposely developed media, i.e. ILM and Colicult are shown to reconcile the requirements of growth support with that of optimal luminescent properties.

Bacteriological Techniques↗
PubMedDate not supplied

Changes of structure and energy on the route from dioxetane to carbonyl products. A quantum chemical study.

Energy diagrams, changes of geometry and bond orders were calculated semi-empirically for the thermolysis of 1,2-dioxetane. Stretching of the O-O bond, then of the C-C bond and distortion of the whole quadrangular structure make major, but different, contributions to the reaction coordinate on the path to formaldehyde. The activation barrier represents a vast region where the gaps between the ground and excited states are small, and this favours horizontal radiationless transitions leading to the excitation of a product. The results show that semi-empirical calculations may help to provide better insight into the nature and mechanism of the chemiluminescence excitation.

Heterocyclic Compounds↗
PubMed2000

In-line coupling capillary electrochromatography with amperometric detection for analysis of explosive compounds.

Amperometric detection at a bare gold electrode has been in-line coupled with capillary electrochromatography (CEC) for analysis of nitroaromatic and nitroamine explosives in contaminated soils and ground water. The CEC column packed with 3 microm C18 particles performed best using a mobile phase containing 70-80% methanol, 30 or 20% water, 5 mM sodium dodecyl sulfate (SDS) and 10mM 2-(N-morpholino)ethanesulfonic acid (MES). In contrast, the separation column packed with 1.5 km C18 particles exhibited the best separation when only 30% methanol was added to a mobile phase containing 70% water, 7 mM SDS, and 10 mM MES. The detection, based on electrochemical reduction of the explosives (-0.7 or -1 V vs. Ag/AgCl, depending upon the level of methanol in the mobile phase), was compatible with such mobile phases. The detection limits for 13 explosives ranged from 100 to 200 ppb, i.e., about twofold better than those obtained with electrokinetic chromatography (EKC)/amperometric detection. From an operational viewpoint, exhaustive column conditioning was a prerequisite and care should be taken to prevent bubble formation and current breakdown during the course of separation. The CEC column equipped with amperometric detection successfully measured explosives in ground water and extracts prepared from contaminated soils and the results obtained agreed well with those of the U.S. Environmental protection Agency (EPA) method.

Azocines↗
PubMedDate not supplied

Synthesis and chemiluminescent decomposition of spiro[1, 2-dioxetane-3,6'-benzo(c)chromene]s.

Two spiro[1,2-dioxetane-3,6'-benzo(c)chromene]s bearing a t-butyldimethylsiloxy as a trigger at the 10'- or 2'-position were synthesized. On treatment with tetrabutylammonium fluoride in DMSO at 25 degrees C, the 10'-siloxyspiro[1,2-dioxetane-3, 6'-benzo(c)chromene] decomposed rapidly to afford a flash of blue light. The CIEEL decay of this spirochromenedioxetane was also induced by basic silica gel in hexane. By contrast, TBAF-induced decomposition of an analogous spiro[1,2-dioxetane-3, 6'-benzo(c)chromene] with a trigger at the 2'-position, resulted in emission of yellow light with very low efficiency.

Benzopyrans↗
PubMedDate not supplied

Synthesis of 3-ethoxy-4,4-diisopropyl-1,2-dioxetanes bearing a benzo(b)furan-2-yl or a benzo(b)thiophen-2-yl group: CIEEL-active dioxetanes emitting red light.

Low-temperature singlet oxygenation of 1-ethoxy-2, 2-diisopropylethylenes substituted with a benzo(b)furanyl or a benzo(b)thiophenyl group bearing a t-butyldimethylsiloxy at the 5-, 6- or 7-position of the aromatic ring afforded the corresponding 1, 2-dioxetanes in moderate to high yields. On treatment with tetrabutylammonium fluoride in DMSO, dioxetanes with a trigger (siloxy group) at the 5- or 7-position of the aromatic ring decomposed to emit red light (lambda(max) = 615-628 nm), irrespective of the aromatic ring being benzofuran or benzothiophene. For both series of benzofuran-analogues and benzothiophene-analogues, an 'odd/even' relationship between the position of an oxyanion on the aromatic ring relative to the attachment point to the dioxetane and the chemiluminescent properties, lambda(max), Phi(CL), and t(1/2), is observed, as in the case for dioxetanes bearing a phenolic or naphtholic substituent.

Ethers, Cyclic↗
PubMed1994

Comparative toxicity studies of yttrium-90 MX-DTPA and 2-IT-BAD conjugated monoclonal antibody (BrE-3).

BACKGROUND: BrE-3 is monoclonal antibody that has promise for imaging and therapy of human adenocarcinoma. Because of observations in therapeutic trials of yttrium-90 (90Y) escape from radioimmunoconjugates and uptake by the skeleton with resultant bone marrow toxicity, the authors attempted to evaluate the importance of this factor by a comparison of the LD50 in healthy mice treated with 90Y that had been chelated with either of two high affinity chelators, methylbenzyldiethylene-triaminepentaacetic acid (MX-DTPA) or bromoacetamidobenzyl-1,4,7,10-tetraazocyclododecane- N,N',N'',N'''-tetraacetic acid (BAD). METHODS AND RESULTS: Bone marrow hematopoietic toxicity was dose-limiting and the source of death for both chelators. The LD50 for 90Y-BrE-3-MX-DTPA was 220.9 microCi, and that for 90Y-BrE-3-2IT-BAD and was 307.8 microCi. Whole-body autoradiography revealed substantially greater uptake of 90Y in the skeleton when MX-DTPA was used as the chelator. CONCLUSIONS: These observations suggest that 90Y escape to bone is a significant factor in the maximum tolerated dose of radioimmunoconjugate that can be used in therapeutic trials. These results probably underestimate the importance of 90Y escape since 90Y in the skeleton of patients is likely to be more significant than in mice because more of the 90Y energy is absorbed in the marrow of larger species.

Animals↗
PubMed2000

An azacrown-functionalized peptide as a metal ion based catalyst for the cleavage of a RNA-model substrate.

The previously synthesized, terminally blocked heptapeptide Ac-Aib-ATANP-Aib-Aib-ATANP-Aib-Aib-OMe (1a), where ATANP is (S)-2-amino-3-[1-(1,4,7-triazacyclononane)]propanoic acid and Aib is alpha-aminoisobutyric acid, which is soluble in neutral water where it largely adopts a 3(10)-helical conformation, has been studied, as bimetallic complex [metal ions: Cu(II), Ni(II), Zn(II)], for the transphosphorylation catalysis of the RNA-model substrate 2-(hydroxypropyl)-p-nitrophenyl phosphate (HPNP). A detailed analysis was carried out with the Zn(II) dinuclear complex. Comparison with the mononuclear Zn(II) complex with 1,4,7-triazacyclononane (3) points to cooperativity between the two Zn(II) ions in the process catalyzed by 1a-2Zn(II). On the contrary, the dinuclear Zn(II) complex of dipeptide Ac-(ATANP)(2)-OMe (2), lacking any ordered conformation, is less active than 3-Zn(II). The kinetic analysis suggests the following: (a) the peptide is conformationally very robust and does not loose activity up to 50 degrees C; (b) the substrate binds to the peptide-Zn(II) complex, although not all modes of complexation allow us to take advantage of the cooperativity between the two metal centers. The maximum rate acceleration estimated at pH 7 for the fully bound substrate is ca. 200-fold compared with the uncatalyzed process.

Alanine↗
PubMed2001

[DOTA-bis(amide)]lanthanide complexes: NMR evidence for differences in water-molecule exchange rates for coordination isomers.

Two derivatives of 1,4,7,10-tetraazacyclododecane with trans-acetate and trans-amide side-chain ligating groups have been prepared and their complexes with lanthanide cations examined by multinuclear NMR spectroscopy. These lanthanide complexes exist in aqueous solution as a mixture of slowly interconverting coordination isomers with 1H chemical shifts similar to those reported previously for the major (M) and minor (m) forms of the tetraacetate ([Ln(dota)]-) and tetraamide ([Ln(dtma)]3+) complexes. As in the [Ln(dota)]- and [Ln(dtma)]3+ complexes, the m/M ratio proved to be a sensitive function of lanthanide size and temperature. An analysis of 1H hyperfine shifts in spectra of the Yb3+ complexes revealed significant differences between the axial (D1) and non-axial (D2) components of the magnetic susceptibility tensor anisotropy in the m and M coordination isomers and the energetics of ring inversion and m <==> M isomerization as determined by two-dimensional exchange spectroscopy (EXSY). (17)O shift data for the Dy3+ complexes showed that both have one inner-sphere water molecule. A temperature-dependent (17)O NMR study of bulk water linewidths for solutions of the Gd3+ complexes provided direct evidence for differences in water exchange rates for the two coordination isomers. The bound-water lifetimes (tauM298) in the M and m isomers of the Gd3+ complexes ranged from 1.4-2.4 micros and 3-14 ns, respectively. This indicates that 1) the inner-sphere water lifetimes for the complexes with a single positive charge reported here are considerably shorter for both coordination isomers than the corresponding values for the [Gd(dtma)]3+ complex with three positive charges, and 2) the difference in water lifetimes for M and m isomers in these two series is magnified in the [Gd[dota-bis(amide)]] complexes. This feature highlights the remarkable role of both charge and molecular geometry in determining the exchange rate of the coordinated water.

Chelating Agents↗
PubMed2001

Inulin as a carrier for contrast agents in magnetic resonance imaging.

Magnetic resonance angiography (MRA) has put forth an impetus for the development of macromolecular GdIII complexes that have a prolonged lifetime in the vascular system. Herein, we report the synthesis and GdIII complexation of a new sugar conjugate based on inulin and the DO3A ligand (DO3A = 1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acid). Two API-DO3ASQ conjugates (API = O-(aminopropyl)inulin, SQ = squaric acid = 3,4-dihydroxy-3-cyclobutene-1,2-dione) with different degrees of substitution (ds = 0.7 and ds = 1.5) were prepared from API by using the diethyl ester of squaric acid as a linking agent for the DO3A chelate. The efficacies of the resulting GdIII compounds were evaluated by investigation of their water 1H longitudinal-relaxation-rate enhancements at variable field (NMRD). A dramatic increase in relaxivity was observed in the more highly substituted conjugate (ds = 1.5); this prompted us to do a variable-temperature (17)O study in order to further characterize the relaxation parameters involved in this system. [Gd(API-DO3ASQ)] shows promising properties for application as a contrast agent for MRI.

Chelating Agents↗
PubMed1993

Examples of evolution of microstructure in ceramics and composites.

In this article we describe a number of studies involving the direct observation of microstructural evolution. In general these investigations were carried out to establish the mechanistic paths involved. The materials studied range from fibers being evaluated for use in high-temperature ceramic composites to energetic materials used as propellants. In particular we discuss the room temperature imaging of materials difficult to image by conventional means and the use of the chamber atmosphere to influence microstructural evolution. Imaging of hydroxyapatite formed by chemical means is briefly described as an example of a difficult microstructure. Microstructural evolution during calcium aluminate cement hydration relies on the chamber atmosphere to control moisture loss from the hydrating specimens. In some instances microstructural evolution with heating occurred independently of the chamber atmosphere. Grain growth in PZT films formed by sol-gel processes depends strongly on temperature but does not appear to depend on the chamber atmosphere. This is also the case for the combustion of nitroamine propellants in that their combustion does not depend on access to an external source of oxygen. In other studies, the chamber atmosphere played an indirect role in determining microstructure. However, the mechanistic path driving microstructural evolution in copper-based inks used as conductive paths on electronic substrates is atmosphere dependent. These inks are formulated from copper powder, glass, and an organic binder, and the interaction of the binder with an oxidizing atmosphere allows it to be burned out before significant interaction occurs between the copper powder and the glass. Finally, the microstructural variations during the oxidation of structural composites at high temperature were used to allow assessments of their likely failure mechanisms.

Animals↗
PubMed1986

Magnetic field dependence of solvent proton relaxation rates induced by Gd3+ and Mn2+ complexes of various polyaza macrocyclic ligands: implications for NMR imaging.

The magnetic field dependence of the solvent water proton longitudinal relaxation rate 1/T1 (the NMRD profile) has been measured for solutions of chelates of Gd3+ and Mn2+ ions with two different polyaza macrocyclic ligands: 1,4,7-triazacyclononane-N,N',N",-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA). Studies were carried out mainly near physiological pH, but the pH dependence was also examined in some cases. The results are compared with published data for complexes of Gd3+ and Mn2+ ions with ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA). Competition experiments for the NOTA and DOTA chelates with EDTA and DTPA were also performed. It is found that, over the field range in which NMR imaging is currently being done, different symmetries of otherwise similar chemical ligands can alter 1/T1 of solvent protons by factors of up to three. The ligand environment can influence the relaxation times of the electronic spin moments of the ions, as well as their coordination number, thereby changing both the inner and outer sphere contributions to the relaxivities of the complexes. The relevance of these results to questions of efficiency and toxicity of these chelates as agents for enhancement of contrast in NMR images is discussed.

Animals↗
PubMed1986

Gd(DOTA): an alternative to Gd(DTPA) as a T1,2 relaxation agent for NMR imaging or spectroscopy.

Methods have been devised for obtaining gadolinium(III) complexes of the ligands NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid), DOTA (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), TETA (1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid), and DTPA (diethylenetriaminepentaacetic acid) as solids for use as pharmaceuticals. Their effectiveness as in vitro and in vivo contrast agents for NMR imaging or T1,2 relaxation agents for spectroscopy has been investigated. The Gd(DOTA) complex was shown to be a more stable alternative to Gd(DTPA) by serum stability studies and measurement of stability constants. Images of tumors grown in athymic mice were obtained by NMR after injection of Gd(DOTA) and Gd(DTPA).

Animals↗
PubMed1995

Enhancement of enzyme-activated 1,2-dioxetane chemiluminescence in membrane-based assays.

Processes for enhancing the chemiluminescent signal generated by enzyme-activated 1,2-dioxetanes have been developed for membrane-based assays in which detection is done using a charge-coupled device (CCD) camera or X-ray film. The enhancement is demonstrated using slot-blots of biotinylated lambda DNA in conjunction with an avidin-alkaline phosphatase conjugate. For detection with a CCD camera, the nylon membrane is dried after processing and incubation in dioxetane substrate solution and heated to temperatures of 50 to 80 degrees C during detection. Up to a 100-fold signal increase is obtained using this enhancement process compared to the conventional detection procedure, in which the blot is kept saturated with substrate solution in a sealed plastic bag during detection. For detection with X-ray film, a fivefold increase in signal intensity is realized by drying the membrane before exposure to the film. These enhancement processes greatly reduce the time required for detection in membrane-based assays.

Heterocyclic Compounds↗
PubMed1995

Imaging and quantitation of chemiluminescence using photoexcitable storage phosphor screen.

A novel storage phosphor (SrS:Ce,Sm) imaging screen optimized for the detection of luminescence has been developed. When coupled with an appropriate scanning system, this screen exhibits the following characteristics: (i) a range of visible light detection between 400 and 500 nm with a peak response at 450 nm; (ii) sensitivity comparable to X-ray film; (iii) 200-microns resolution; (iv) linear dynamic range greater than four orders of magnitude; and (v) a uniformity of response of +/- 1.32% coefficient of variation. These features facilitate the detection and accurate quantitation of light radiation produced from the enzymatic catalysis of chemiluminescent substrates such as 1,2-dioxetanes and luminol. Its suitability for chemiluminescent applications is demonstrated by the analysis of cosmid hybridization and enzyme-linked immunosorbent assay samples.

Alkaline Phosphatase↗
PubMed1998

Development of a soil extraction procedure for ecotoxicity characterization of energetic compounds.

The acetonitrile-sonication extraction method (US EPA Method 8330) associated with aquatic-based toxicity tests was examined to study the ecotoxicity of energetic substances in soil. Three studies were carried out: (1) toxicological characterization of different energetic substances to select a representative toxicant and to validate the choice of bioassays; (2) choice of an appropriate solvent to transfer acetonitrile extracts to the bioassay incubation media; and (3) optimization of Method 8330 using soil samples spiked with the toxicant. Initial studies indicated that pure 2,4,6-trinitrotoluene (TNT) was toxic to Vibrio fischeri [Microtox; IC50 (15 min) of 4.2 microM], whereas RDX was less toxic (IC20 = 181 microM) and HMX was not toxic up to its limit of water solubility (< 22 microM). Selected pure TNT metabolites were less toxic than TNT. Similar results were found using the 96-h Selenastrum capricornutum growth inhibition test. The toxicity of pure TNT in different solvents (acetonitrile, acetone, and DMSO) and that from Method 8330-extracted TNT-spiked soil samples were compared to TNT dissolved in water. Data indicated that DMSO was the most appropriate solvent to transfer the acetonitrile extracts. A modified Method 8330 may be used in conjunction with bioassays and chemical analyses to examine the ecotoxicity of soils contaminated with energetic substances.

Acetone↗