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Breton F.,University of Waterloo | Monton M.R.N.,University of Waterloo | Mullett W.M.,MDS Nordion | Pawliszyn J.,University of Waterloo
Analytica Chimica Acta | Year: 2010

We present a novel way to prepare SPME fibers using a silicate entrapment of porous particles, followed by derivatization using classical organosilane chemistry. The fibers provide a good platform for on-fiber derivatization of desired extraction phases while providing porosity necessary for high extractions capacities. The porous network was created using potassium silicate and porous silica particles. Fibers derivatized using n-butyl, n-octyl, n-octadecyl and n-triacontyl groups were shown to extract benzodiazepines successfully. The coatings were determined to have an average thickness of ca. 8μm, as determined by a scanning electron microscope, permitting equilibrium times as fast as 2min. The fibers also showed very good ruggedness towards a vast range of solvents and prolonged use. It was determined that greater extraction efficiencies could be obtained using triacontyl as an extraction phase. The C18 and C30 fibers were also found to provide good linearity (>0.99) for the model analytes over two orders of magnitude, with limits of detection in the sub ngmL-1 levels. C30 fibers were used to establish a correlation between structurally diverse β-blockers and their literature reported LogP values. The C30 fibers provided a good correlation (R2=0.9255) between β-blockers ranging in hydrophobicity from LogPliterature 0.16-4.15 and their respective experimentally determined LogKspme values. © 2010 Elsevier B.V. Source

Mds Nordion | Date: 2001-03-07

Industrial equipment and apparatus, namely, conveyors, power operated source hoists and mechanical load and unload stations using radiation energy for disinfestation and for reducing spoilage organisms and pathogenic organisms in food, for sterilization of medical disposable products, for disposing of biological wastes and application to microbial reduction in cosmetics and pharmaceuticals. Industrial electronic processing equipment, namely, control consoles for industrial equipment, programmable logic control systems consisting primarily of computer software and hardware, video monitor and blank magnetic data carriers used in conjunction with irradiation equipment for disinfestation and for reducing spoilage organisms and pathogenic organisms in food, for sterilization and medical disposable products and for disposing of biological waste.

Ferreira C.L.,MDS Nordion | Yapp D.T.T.,British Columbia Cancer Agency Research Center | Yapp D.T.T.,University of British Columbia | Crisp S.,MDS Nordion | And 7 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2010

Purpose: Improved bifunctional chelates (BFCs) are needed to facilitate efficient 64Cu radiolabeling of monoclonal antibodies (mAbs) under mild conditions and to yield stable, target-specific agents. The utility of two novel BFCs, 1-Oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7, 10-triacetic acid (p-SCN-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA), for mAb imaging with 64Cu were compared to the commonly used S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane- tetraacetic acid (p-SCN-Bn-DOTA). Methods: The BFCs were conjugated to trastuzumab, which targets the HER2/neu receptor. 64Cu radiolabeling of the conjugates was optimized. Receptor binding was analyzed using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER2/neu-positive or HER2/neu-negative tumors. Results: 64Cu-Oxo-DO3A- and PCTA-trastuzumab were prepared at room temperature in >95% radiochemical yield (RCY) in <30 min, compared to only 88% RCY after 2 h for the preparation of 64Cu-DOTA-trastuzumab under the same conditions. Cell studies confirmed that the immunoreactivity of the mAb was retained for each of the bioconjugates. In vivo studies showed that 64Cu-Oxo-DO3A- and PCTA-trastuzumab had higher uptake than the 64Cu-DOTA-trastuzumab at 24 h in HER2/neu-positive tumors, resulting in higher tumor to background ratios and better tumor images. By 40 h all three of the 64Cu-BFC-trastuzumab conjugates allowed for clear visualization of the HER2/neu-positive tumors but not the negative control tumor. Conclusion: The antibody conjugates of PCTA and Oxo-DO3A were shown to have superior 64Cu radiolabeling efficiency and stability compared to the analogous DOTA conjugate. In addition, 64Cu-PCTA and Oxo-DO3A antibody conjugates may facilitate earlier imaging with greater target to background ratios than the analogous 64Cu-DOTA antibody conjugates. © 2010 Springer-Verlag. Source

Boros E.,University of British Columbia | Boros E.,TRIUMF Laboratory Particle and Nuclear Physics | Ferreira C.L.,MDS Nordion | Cawthray J.F.,University of British Columbia | And 6 more authors.
Journal of the American Chemical Society | Year: 2010

We have investigated novel bifunctional chelate alternatives to the aminocarboxylate macrocycles NOTA (N3O3) or DOTA (N 4O4) for application of radioisotopes of Ga to diagnostic nuclear medicine and have found that the linear N4O2 chelate H2dedpa coordinates 67Ga quantitatively to form [67Ga(dedpa)]+ after 10 min at RT. Concentration-dependent coordination to H2dedpa of either 68Ga or 67Ga showed quantitative conversion to the desired products with ligand concentrations as low as 10-7 M. With 68Ga, specific activities as high as 9.8 mCi nmol-1 were obtained without purification. In a 2 h competition experiment against human apo-transferrin, [67Ga(dedpa)]+ showed no decomposition. Two bifunctional versions of H2dedpa are also described, and these both coordinate to 67Ga at RT within 10 min. Complete syntheses, characterizations, labeling studies, and biodistribution profiles of the 67Ga complexes are presented for the new platform chelates. The stability of these platform chelates is higher than that of DOTA. © 2010 American Chemical Society. Source

Ferreira C.L.,MDS Nordion | Lamsa E.,MDS Nordion | Woods M.,MDS Nordion | Duan Y.,Ottawa Heart Institute | And 6 more authors.
Bioconjugate Chemistry | Year: 2010

Ga radioisotopes, including the generator-produced positron-emitting isotope 68Ga (t 1/2 = 68 min), are of increasing interest for the development of new radiopharmaceuticals. Bifunctional chelates (BFCs) that can be efficiently radiolabeled with Ga to yield complexes with good in vivo stability are needed. To this end, we undertook a systematic comparison of four BFCs containing different chelating moieties: two novel BFCs, p-NO 2-Bn-OxO (l-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid) and p-NO 2-Bn-PCTA (3,6,9,15-tetraazabicyclo [9.3.1]pentadeca-l(1.5),11, 13-triene-3,6,9-triacetic acid), and two more commonly used BFCs, p-NO 2-Bn-DOTA (1,4,7,10tetraazacyclododecane-1,4,7,10-tetraacetic acid) and p-NO 2-Bn-NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid). Each BFC was compared with respect to radiolabeling conditions, radiochemical yield, stability, and in vivo clearance properties. p-NO 2-Bn-PCTA, p-NO 2-Bn-OxO, and p-NO 2-Bn-NOTA were all more efficiently radiolabeled with Ga compared to p-NO 2-Bn-DOTA. p-NO 2-Bn-DOTA required longer reaction time, higher concentrations of BFC, or heating to obtain equivalent radiochemical yields. Better stability was observed for p-NO 2-Bn-NOTA and p-NO 2-Bn-PCTA compared to p-NO 2-Bn-DOTA and p-NO 2-Bn-OxO, especially with respect to transmetalation to transferrin. Ga-radiolabled p-NO 2-Bn-OxO was found to be kinetically labile and therefore unstable in vivo. Ga-radiolabeled p-NO 2-Bn-NOTA and p-NO 2-Bn-PCTA were relatively inert, while Ga-radiolabeled p-NO 2-BnDOTA had intermediate stability, losing >20% of Ga in less than one hour when incubated with apo-transferrin. Similar stability differences were seen when incubating at. pH 2. In vivo PET imaging and biodistribution studies in mice showed that 68Ga- radiolabeled p-NO 2-Bn-PCTA, p-NO 2-Bn-NOTA, and p-NO 2-Bn-DOTA all cleared through the kidneys. While there was no statistical difference in the biodistribution results of 68Ga- radiolabeled p-NO 2-Bn-PCTA and p-NO 2-Bn-DOTA, 68Ga-radiolabeled p-NO 2-Bn-NOTA cleared more rapidly from blood and muscle tissue but retained at up to 5 times higher activity in the kidneys. © 2010 American Chemical Society. Source

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