<p>Radioactive substances are used <i>in vivo</i> to localize and characterize malignant tumours, generally by scintigraphic methods. In this context positron emission tomography (PET) in combination with radiolabelled monoclonal antibodies (mAbs) may provide a sensitive and specific method for detection of cancer. Individual dose calculations, based on such PET measurements, may be carried out to predict the possible use of mAbs labelled with therapeutic nuclides. The positron emitter ⁷⁶Br, with a half-life of 16 h, is a well-suited candidate for radiolabelling and PET imaging. One drawback of radiobromine is that bromide, the ultimate catabolite after degradation of brominated mAb, is only tardily excreted from the body and is evenly distributed throughout the extracellular space, thereby increasing the background radioactivity. The aim of this work was to produce ⁷⁶Br-mAb preparations with high accumulation and retention in tumour tissue together with a quick clearance of ⁷⁶Br-labelled catabolites. Furthermore, the possibility to use brominated or iodinated mAbs in combination with PET to predict ²¹¹At-mAb dosimetry was evaluated.</p><p>Monoclonal Abs directed against colorectal cancer were labelled with ⁷⁶Br using the direct Chloramine-T-method or indirectly by labelling the precursor molecule N-succinimidyl para-(tri-methylstannyl) benzoate with ⁷⁶Br, which was subsequently conjugated to the mAbs. Monoclonal Ab A33 labelled with ⁷⁶Br using the two labelling protocols was characterized in vitro and in vivo in a rat tumour xenograft model. The mAb A33 was also labelled with ¹²⁵I for comparison. In addition, mAb A33 was labelled with ²¹¹At, ¹²⁵I and ⁷⁶Br using the indirect labelling protocol and the mAb pharmacokinetics was studied in normal rats in order to estimate if data from brominated or iodinated mAb could be used for dosimetry of ²¹¹At in healthy organs and tissue.</p><p>In conclusion, both direct and indirect labelling resulted in high yields and mAbs with preserved immunoreactivity. <i>In vivo</i> characterization of ⁷⁶Br-brominated mAb A33 showed that the indirect labelling method makes ⁷⁶Br-brominated mAb A33 a promising candidate for tumour imaging with PET due to the faster excretion of radiolabelled catabolites compared with direct bromination. Finally, mAb A33 labelled with ⁷⁶Br and ^124/125I can be used to predict the ²¹¹At dose of astatinated mAb A33 in most organs given that a correction factor is applied for organs with varying uptake.</p>

Bromine compounds play an important role as catalyst of the ozone destruction in both the stratosphere and troposphere. While the impact of bromine species on the chemistry of the stratosphere is known to a large extend, a number of uncertainties remain regarding the sources and sinks of atmospheric bromine as well as the chemistry and impact of bromine species on the troposphere. This work describes remote-sensing observations of bromine monoxide (BrO) derived from scattered sunlight spectra in the ultraviolet region measured by ground-based multi-axis and satellite nadir viewing instruments (GOME and GOME-2). The method of differential optical absorption spectroscopy is used to retrieve the columnar concentration of BrO along the effective light path through the atmosphere. New algorithms to derive vertical columns of BrO resolved into their stratospheric and tropospheric contributions are developed and described. For the ground-based geometry a way was found to determine independently the stratospheric and tropospheric BrO columns from the diurnal variation of the BrO measurements. For the satellite observations, the contribution of the stratospheric BrO to the measured column is estimated using an innovative stratospheric BrO climatology. This climatology is based on a state-of-the-art stratospheric chemical transport model, and explicitly accounts for the impact of atmospheric dynamics and photochemistry on the stratospheric BrO distribution. As for the tropospheric fraction of the measured total BrO column, it is derived using a residual technique accounting for the effects of clouds and surface reflectivity. Supported by an extensive set of correlative data, the results presented here allow to study properly the spatial and temporal evolution of atmospheric BrO at the global scale and enable to better assess the significance of BrO in the polar planetary boundary layer and free-troposphere as well as the contribution from very short-lived brominated sources gases to the stratospheric bromine budget. We also report on the first satellite detection of BrO in a volcanic plume, using GOME-2 measurements. Les composés bromés jouent un rôle important dans la stratosphère et la troposphère en tant que catalyseurs de la destruction d’ozone. Bien que l’impact des espèces bromées sur la chimie de la stratosphère soit largement compris, il reste de nombreuses incertitudes en ce qui concerne les sources et les pertes de brome dans l’atmosphère ainsi qu’à propos de la chimie et de l’impact des espèces bromées sur la troposphère. Le travail présenté dans ce manuscrit porte sur la télédétection du monoxyde de brome (BrO) à partir de spectres du rayonnement solaire diffusé, mesurés dans l’ultraviolet à partir d’instruments au sol de type multi-axis et satellitaires à visée nadir (GOME et GOME-2). La méthode de spectroscopie d’absorption optique différentielle est utilisée pour inverser la colonne intégrée de BrO le long du chemin optique effectif dans l’atmosphère. Nous avons développé de nouveaux algorithmes afin de dériver les colonnes verticales de BrO résolues en leurs contributions stratosphérique et troposphérique. Pour la géométrie d’observation au sol, un moyen a été trouvé pour déterminer indépendamment les colonnes de BrO stratosphérique et troposphérique, et cela à partir de la variation diurne des mesures de BrO. Pour les observations satellitaires, la contribution de la stratosphère à la colonne mesurée de BrO est estimée à partir d’une climatologie innovante de BrO stratosphérique. Cette climatologie est basée sur un modèle de pointe de la chimie et du transport de la stratosphère; par ailleurs, elle tient compte explicitement de l’impact de la dynamique atmosphérique et de la photochimie sur la distribution du BrO dans la stratosphère. La fraction troposphérique de la colonne totale mesurée de BrO est quant à elle dérivée à partir d’une technique résiduelle tenant compte des effets des nuages et de la réflectivité de la surface. Soutenus par un vaste jeu de données corrélatives, les résultats présentés dans ce travail permettent d’étudier de manière appropriée l’évolution spatiale et temporelle du BrO atmosphérique à l’échelle globale. Ces résultats permettent également de mieux estimer l’importance du BrO dans la couche limite planétaire polaire et dans la troposphère libre ainsi que la contribution des précurseurs bromés à temps de vie court sur le budget de brome dans la stratosphère. Nous présentons également la première détection satellitaire de BrO dans un panache volcanique, à l’aide de mesures effectuées avec l’instrument GOME-2.

Radioactive substances are used in vivo to localize and characterize malignant tumours, generally by scintigraphic methods. In this context positron emission tomography (PET) in combination with radiolabelled monoclonal antibodies (mAbs) may provide a sensitive and specific method for detection of cancer. Individual dose calculations, based on such PET measurements, may be carried out to predict the possible use of mAbs labelled with therapeutic nuclides. The positron emitter 76Br, with a half-life of 16 h, is a well-suited candidate for radiolabelling and PET imaging. One drawback of radiobromine is that bromide, the ultimate catabolite after degradation of brominated mAb, is only tardily excreted from the body and is evenly distributed throughout the extracellular space, thereby increasing the background radioactivity. The aim of this work was to produce 76Br-mAb preparations with high accumulation and retention in tumour tissue together with a quick clearance of 76Br-labelled catabolites. Furthermore, the possibility to use brominated or iodinated mAbs in combination with PET to predict 211At-mAb dosimetry was evaluated. Monoclonal Abs directed against colorectal cancer were labelled with 76Br using the direct Chloramine-T-method or indirectly by labelling the precursor molecule N-succinimidyl para-(tri-methylstannyl) benzoate with 76Br, which was subsequently conjugated to the mAbs. Monoclonal Ab A33 labelled with 76Br using the two labelling protocols was characterized in vitro and in vivo in a rat tumour xenograft model. The mAb A33 was also labelled with 125I for comparison. In addition, mAb A33 was labelled with 211At, 125I and 76Br using the indirect labelling protocol and the mAb pharmacokinetics was studied in normal rats in order to estimate if data from brominated or iodinated mAb could be used for dosimetry of 211At in healthy organs and tissue. In conclusion, both direct and indirect labelling resulted in high yields and mAbs with preserved immunoreactivity. In vivo characterization of 76Br-brominated mAb A33 showed that the indirect labelling method makes 76Br-brominated mAb A33 a promising candidate for tumour imaging with PET due to the faster excretion of radiolabelled catabolites compared with direct bromination. Finally, mAb A33 labelled with 76Br and 124/125I can be used to predict the 211At dose of astatinated mAb A33 in most organs given that a correction factor is applied for organs with varying uptake.

The use of positron emission tomography (PET) has so far mainly been limited to a few nuclides with short half-lives such as 11C and 18F. Certain applications require nuclides with longer half-lives, such as 76Br and 52Fe. In radionuclide therapy positron emitting analogues of therapeutic nuclides, such as 110mIn, or daughter nuclides, such as 134La, can enable improved dosimetry with the use of PET. A challenge associated with the use of these positron emitters is that they emit gamma radiation in cascade with positrons, which complicates quantitative PET imaging. Other possible problems are the high energies of the emitted positrons, and the decay of 52Fe to the short-lived positron emitter 52mMn. Performance measurements were made to investigate the effects of these decay characteristics on the quantitative accuracy, spatial resolution, and other parameters of PET. The distribution of gamma radiation coincidences in PET data was studied and correction methods were implemented and evaluated. PET resolution degrades with 1-2 mm for the studied nuclides in comparison with 18F. The implemented sinogram tail fit and delayed coincidence based gamma radiation coincidence correction methods lead to a quantitative accuracy similar as for 18F and to improved image contrast. Standard dead time corrections are not adequate for gamma-emitting nuclides. Noise equivalent count rates are considerably lower for 76Br than for 18F at clinically relevant radioactivity concentrations. A method to correct 52Fe patient data for the contribution of 52mMn is discussed. The use of 110mIn is evaluated in a patient study and compared to SPECT imaging with 111In. A dosimetric and PET evaluation of the use of 134Ce/134La for radionuclide therapy and dosimetry is presented. Dosimetry of 76Br-labelled antibodies is studied in a pig model. Finally, the possibility to use PET for dosimetry during radionuclide therapy is studied and a nonuniform dose calculation program is presented.

Oscillator strengths and transition energies are calculated for several mono-substitutes of benzene and naphthalene molecules. The substituents investigated are chlorine, bromine and iodine. Calculations for these molecules are presented, at the Hartree-Fock and DFT level of theory. The functional used in DFT is CAM-B3LYP.

Two new analytical methodologies were developed for chlorine and bromine stable isotope analyses of inorganic samples by Continuous-Flow Isotope Ratio Mass Spectrometry (CF-IRMS) coupled with gas chromatography (GC). Inorganic chloride and bromide were precipitated as silver halides (AgCl and AgBr) and then converted to methyl halide (CH3Cl and CH3Br) gases and analyzed. These new techniques require small samples sizes (1.4 µmol of Cl- and 1 µmol of Br-). The internal precision using pure CH3Cl gas is better than ∓0.04 ‰ (∓STDV) while the external precision using seawater standard is better than ∓0.07 ‰ (∓STDV). The internal precision using pure CH3Br gas is better than ∓0.03 ‰ (∓STDV) and the external precision using seawater standard is better than ∓0.06 ‰ (∓STDV). Moreover, the sample analysis time is much shorter than previous techniques. The analyses times for chlorine and bromine stable isotopes are 16 minutes which are 3-5 times shorter than all previous techniques. Formation waters from three sedimentary settings (the Paleozoic sequences in southern Ontario and Michigan, the Williston Basin and the Siberian Platform) were analyzed for 37Cl and 81Br isotopes. The δ37Cl and δ81Br values of the formation waters from these basins are characterized by large variations (between -1.31 ‰ and +1.82 ‰ relative to SMOC and between -1.50 ‰ and +3.35 ‰ relative to SMOB, respectively). A positive trend between δ81Br and δ37Cl values was found in all basins, where an enrichment of δ81Br is coupled by an enrichment of δ37Cl. In the Paleozoic sequences in southern Ontario and Michigan, the δ37Cl and δ81Br signatures of formation water collected from northwest of the Algonquin Arch are distinct from those collected from southeast of the Arch. All of the brines from the northwest of the Algonquin Arch are characterized by depleted isotopic values in comparison with the isotopic values from the brines from southeast of the Arch. The δ81Br signatures of the two brines show total separation with no overlaps. The δ37Cl values show some overlap between the two groups. One of the scenarios that can be put forward is that the Arch forms a water divide, where sediments southeast of the Arch are dominated by Appalachian Basin formation waters, and the sediments located northwest of the Arch are dominated by the Michigan Basin formation waters. The δ81Br and δ37Cl signatures of the Williston Basin brines suggest the existence of several different brines that are isotopically distinct and located in different stratigraphic units, even though they are chemically similar. The relatively wide range of δ37Cl and δ81Br of the formation waters suggests that the ocean isotopic signatures were variable over geologic time. A seawater temporal curve for δ81Br and δ37Cl was proposed with a larger variation of δ81Br in comparison with δ37Cl. The isotopic variations of these two elements agree very well with 87Sr/86Sr seawater variation during the same period. In general, the use of chlorine and bromine stable isotopes can be very useful in assessing the origin and the evolutionary processes involved in evolving formation waters and also in distinguishing different brines (end members). Furthermore, they can be employed to investigate the hydrogeological dynamics of sedimentary basins.

Two new analytical methodologies were developed for chlorine and bromine stable isotope analyses of inorganic samples by Continuous-Flow Isotope Ratio Mass Spectrometry (CF-IRMS) coupled with gas chromatography (GC). Inorganic chloride and bromide were precipitated as silver halides (AgCl and AgBr) and then converted to methyl halide (CH3Cl and CH3Br) gases and analyzed. These new techniques require small samples sizes (1.4 µmol of Cl- and 1 µmol of Br-). The internal precision using pure CH3Cl gas is better than ∓0.04 ‰ (∓STDV) while the external precision using seawater standard is better than ∓0.07 ‰ (∓STDV). The internal precision using pure CH3Br gas is better than ∓0.03 ‰ (∓STDV) and the external precision using seawater standard is better than ∓0.06 ‰ (∓STDV). Moreover, the sample analysis time is much shorter than previous techniques. The analyses times for chlorine and bromine stable isotopes are 16 minutes which are 3-5 times shorter than all previous techniques. Formation waters from three sedimentary settings (the Paleozoic sequences in southern Ontario and Michigan, the Williston Basin and the Siberian Platform) were analyzed for 37Cl and 81Br isotopes. The δ37Cl and δ81Br values of the formation waters from these basins are characterized by large variations (between -1.31 ‰ and +1.82 ‰ relative to SMOC and between -1.50 ‰ and +3.35 ‰ relative to SMOB, respectively). A positive trend between δ81Br and δ37Cl values was found in all basins, where an enrichment of δ81Br is coupled by an enrichment of δ37Cl. In the Paleozoic sequences in southern Ontario and Michigan, the δ37Cl and δ81Br signatures of formation water collected from northwest of the Algonquin Arch are distinct from those collected from southeast of the Arch. All of the brines from the northwest of the Algonquin Arch are characterized by depleted isotopic values in comparison with the isotopic values from the brines from southeast of the Arch. The δ81Br signatures of the two brines show total separation with no overlaps. The δ37Cl values show some overlap between the two groups. One of the scenarios that can be put forward is that the Arch forms a water divide, where sediments southeast of the Arch are dominated by Appalachian Basin formation waters, and the sediments located northwest of the Arch are dominated by the Michigan Basin formation waters. The δ81Br and δ37Cl signatures of the Williston Basin brines suggest the existence of several different brines that are isotopically distinct and located in different stratigraphic units, even though they are chemically similar. The relatively wide range of δ37Cl and δ81Br of the formation waters suggests that the ocean isotopic signatures were variable over geologic time. A seawater temporal curve for δ81Br and δ37Cl was proposed with a larger variation of δ81Br in comparison with δ37Cl. The isotopic variations of these two elements agree very well with 87Sr/86Sr seawater variation during the same period. In general, the use of chlorine and bromine stable isotopes can be very useful in assessing the origin and the evolutionary processes involved in evolving formation waters and also in distinguishing different brines (end members). Furthermore, they can be employed to investigate the hydrogeological dynamics of sedimentary basins.

No description available.

Oxidation of aqueous bromide into reactive, gas-phase bromine species has been of interest since the 1980’s, when the presence of bromine in the Arctic boundary layer was linked to ozone depletion events. We have investigated two different mechanisms for Br2 release from sea ice. We have shown that nitrate in sea ice can photolyze to produce OH, which can go on to form gas-phase Br2. This reaction is analogous to a known reaction that occurs in the aqueous phase. We have also investigated Br2 production from a heterogeneous reaction between gas-phase ozone and sea ice/seawater. We have determined ozone’s reactive uptake coefficient, and have shown how it varies with temperature, bromide concentration, ozone concentration and acidity. We have been able to decouple the bulk aqueous chemistry that occurs from the Langmuir-Hinshelwood surface chemistry, and quantify the relative contribution of each.

Oxidation of aqueous bromide into reactive, gas-phase bromine species has been of interest since the 1980’s, when the presence of bromine in the Arctic boundary layer was linked to ozone depletion events. We have investigated two different mechanisms for Br2 release from sea ice. We have shown that nitrate in sea ice can photolyze to produce OH, which can go on to form gas-phase Br2. This reaction is analogous to a known reaction that occurs in the aqueous phase. We have also investigated Br2 production from a heterogeneous reaction between gas-phase ozone and sea ice/seawater. We have determined ozone’s reactive uptake coefficient, and have shown how it varies with temperature, bromide concentration, ozone concentration and acidity. We have been able to decouple the bulk aqueous chemistry that occurs from the Langmuir-Hinshelwood surface chemistry, and quantify the relative contribution of each.