Browsing by Author "Smith, SV"

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    Capture of radioactive cesium and iodide Ions from water by using titanate nanofibers and nanotubes
    (Wiley-Blackwell, 2011-01-01) Yang, D; Sarina, S; Zhu, HW; Liu, HY; Zheng, Z; Xie, M; Smith, SV; Komarneni, S
    Radioactive Cs+ and I− ions are the products of uranium fission, and can be easily dissolved in water during an accident at a nuclear reactor, such as those that occurred at Chernobyl in 1986, at Three Mile Island in Pennsylvania in 1979, and in 2011 at Fukushima, Japan. In 2009, leaks of radioactive materials such as 137Cs and 131I isotopes also occurred during minor accidents at nuclear power stations in Britain, Germany, and the U.S. These leaks have raised concerns about exposure levels in the nearby communities because it is feared that these fission products could make their way into the food chain when present in waste water. Radioactive iodine is also used in the treatment of thyroid cancer, and, as a result, radioactive wastewater is discharged by a large number of medical research institutions.1 The wide use of radioisotopes requires effective methods to manage radioactive waste, and methods currently used are complex and extremely costly.2 Herein we demonstrate a potentially cost-effective method to remediate 137Cs+ and 131I− ions from contaminated water by using the unique chemistry of titanate nanotubes and nanofibers, which can not only chemisorb these ions but efficiently trap them for safe disposal. © 2011, Wiley-Blackwell.
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    Cell labeling: tracking, viability and function
    (Edizioni Minerva Medica, 2005-12-01) Smith, SV
    The rapid progress in research of cell therapy for Parkinson's and Alzheimer's disease, cardiology and cancer has raised considerable excitement and controversy in recent times. In countries such as the UK, Sweden, Singapore, Korea, Japan and Australia, public dicussion has helped to clarify the regulatory framework for their stem cell research. Unfortunately the controversy continues in the US and is expected to significantly impact on the commercialization of much of this technology. © 2005, Edizioni Minerva Medica
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    Clay particles - potential of positron annihilation lifetime spectroscopy (PALS) for studying interlayer spacing
    (Institute of Physics, 2010-08-01) Fong, N; Guagliardo, P; Williams, J; Musumeci, AW; Martin, DJ; Smith, SV
    Characterisation of clays is generally achieved by traditional methods, such as X-ray diffraction (XRD) and transmission electron microscopy (TEM). However, clays are often difficult to characterise due to lack of long-range order, thus these tools are not always reliable. Because interlayer spacing in clays can be adjusted to house molecules, there is growing interest to use these materials for drug delivery. Positron annihilation lifetime spectroscopy (PALS) was examined as an alternative tool to characterise a series of well-known clays. XRD of two layered double hydroxides; MgAl-LDH and MgGd-LDH, natural hectorite, fluoromica and laponite, and their PALS spectra were compared. XRD data was used to calculate the interlayer d- spacing in these materials and results show a decrease in interlayer spacing as the heavy metal ions are substituted for those of large ionic radii. Similar results were obtained for PALS data. This preliminary study suggests PALS has potential as a routine tool for characterising clay particles. Further work will examine the sensitivity and reliability of PALS to percent of metal doping and hydration in clay microstructure. © 2020 IOP Publishing
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    Communicating across the boundaries
    (Edizioni Minerva Medica, 2006-12) Duatti, A; Smith, SV
    Science is a method for investigating natural phenomena. A scientific theory is essentially a set of rules that are expressed through a formal language composed of different symbols. In a scientific language each word (defined as a collection of symbols) has a definite meaning, and should provide the most precise and extensive information within the theory. Thus, in science it is essential that we communicate accurately our work. This can be difficult as everday languages continue to change and the structure for communicating has become quite more amorphous. As a result the freedom to express oneself or take poetic license can result in a lack of clarity across scientific disciplines. © 2006, Edizioni Minerva Medica
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    Feasibility of incorporating cations and anions expected in radioactive waste streams in metakaolin-based geopolymers.
    (Electrical Components International, 2007-03-25) Perera, DS; Vance, ER; Aly, Z; Fuchs, A; Kiyama, S; Davis, J; Smith, SV
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    Imagine the imagery: opportunities and challenges
    (Edizioni Minerva Medica, 2008-09) Cutler, CS; McQuarrie, S; Smith, SV
    This special edition of the Quarterly Journal of Nuclear Medicine and Molecular Imaging captures the outcomes of the workshop organized by the International Association of Radiopharmacology on "Design of in vitro and and in vivo studies - Opportunities and Challenges" held in Aachen, Germany on May 1, 2007 as part of the 17th International Symposium of Radiopharmaceutical Sciences.
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    Imaging cancer using PET - the effect of the bifunctional chelator on the biodistribution of a 64Cu-labeled antibody.
    (Elsevier, 2011-01-01) Dearling, JLJ; Voss, SD; Dunning, P; Snay, E; Fahey, F; Smith, SV; Huston, JS; Meares, CF; Treves, ST; Packard, AB
    Use of copper radioisotopes in antibody radiolabeling is challenged by reported loss of the radionuclide from the bifunctional chelator used to label the protein. The objective of this study was to investigate the relationship between the thermodynamic stability of the 64Cu-complexes of five commonly used bifunctional chelators (BFCs) and the biodistribution of an antibody labeled with 64Cu using these chelators in tumor-bearing mice. © 2011, Elsevier
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    Insight into the mechanisms of metal ion binding in hexagonal tungsten bronze
    (American Physical Society, 2006-03) Kennedy, SJ; Smith, SV; Avdeev, M; Fuchs, A
    Tungsten trioxides and their alkali-metal-intercalated products MzWO3+ show potential for application in electrodes, as ion exchangers, catalysts and the treatment of radioactive waste. Hexagonal tungsten bronze (HTB) was selected for the present work because its structure features hexagonal channels, of diameter ∼0.54 nm, that may be useful for selective and reversible binding of metal ions. X-ray and neutron powder diffraction were used to provide an insight into the mechanisms of metal ion binding of the Mo doped HTB's. Combined Rietveld refinement of the X-ray and neutron diffraction shows that doping with Mo degrades the crystallinity of HTB, in particular by creating a high degree of disorder in the a-b planes. Structural information combined with solution chemistry indicates several potential mechanisms of binding and metal ion exchange sites. This type of investigation provides invaluable information for new strategies in the design of inorganic sorbents and their optimization for metal ion separation.
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    Investigating the binding properties of porous drug delivery systems using nuclear sensors (radiotracers) and positron annihilation lifetime spectroscopy – predicting conditions for optimum performance
    (Royal Society Chemistry, 2011-01-01) Mume, E; Lynch, DE; Uedono, A; Smith, SV
    Understanding how the size, charge and number of available pores in porous material influences the uptake and release properties is important for optimising their design and ultimately their application. Unfortunately there are no standard methods for screening porous materials in solution and therefore formulations must be developed for each encapsulated agent. This study investigates the potential of a library of radiotracers (nuclear sensors) for assessing the binding properties of hollow silica shell materials. Uptake and release of Cu2+ and Co2+ and their respective complexes with polyazacarboxylate macrocycles (dota and teta) and a series of hexa aza cages (diamsar, sarar and bis-(p-aminobenzyl)-diamsar) from the hollow silica shells was monitored using their radioisotopic analogues. Coordination chemistry of the metal (M) species, subtle alterations in the molecular architecture of ligands (Ligand) and their resultant complexes (M-Ligand) were found to significantly influence their uptake over pH 3 to 9 at room temperature. Positively charged species were selectively and rapidly (within 10 min) absorbed at pH 7 to 9. Negatively charged species were preferentially absorbed at low pH (3 to 5). Rates of release varied for each nuclear sensor, and time to establish equilibrium varied from minutes to days. The subtle changes in design of the nuclear sensors proved to be a valuable tool for determining the binding properties of porous materials. The data support the development of a library of nuclear sensors for screening porous materials for use in optimising the design of porous materials and the potential of nuclear sensors for high through-put screening of materials. © 2011, Royal Society of Chemistry
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    An investigation into the potential of SarAr for use in Cu-64 radioimmunotherapy.
    (CSIRO Publishing, 2009-10-13) Di Bartolo, N; Smith, SV; Hetherington, ELR; Sargeson, A
    The B72.3 monoclonal antibody was radiolabelled with 123I, and with 111In and 64Cu, using DTPA and SarAr, respectively. Their biodistribution in tumour-bearing nude mice was used to calculate the dosimetry of their respective therapeutic analogue, using 131I, 90Y, 67Cu, and 64Cu. Two dosimetry models were used: one using the classical approach and a second model that takes into consideration the chemical stability of the radiolabelling methods employed and the biological clearance of each radioimmunoconjugate. Results clearly show that the 64Cu-SarAr-B72.3 could be used as a therapeutic agent and, theoretically, be at least as effective as any of the other therapeutic radionuclides currently studied, such as 131I, 90Y, and 67Cu. © 2009, CSIRO Publishing
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    An investigation into transition metal ion binding properties of silk fibers and particles using radioisotopes
    (Wiley-Blackwell, 2011-03-15) Rajkhowa, R; Naik, R; Wang, L; Smith, SV; Wang, XG
    Silk is a structural protein fiber that is stable over a wide pH range making it attractive for use in medical and environmental applications. Variation in amino acid composition has the potential for selective binding for ions under varying conditions. Here we report on the metal ion separation potential of Mulberry and Eri silk fibers and powders over a range of pH. Highly sensitive radiotracer probes, 64Cu2+, 109Cd2+, and 57Co2+ were used to study the absorption of their respective stable metal ions Cu2+, Cd2+, and Co2+ into and from the silk sorbents. The total amount of each metal ion absorbed and time taken to reach equilibrium occurred in the following order: Cu2+ > Cd2+ > Co2+. In all cases the silk powders absorbed metal ions faster than their respective silk fibers. Intensive degumming of the fibers and powders significantly reduced the time to absorb respective metal ions and the time to reach equilibrium was reduced from hours to 5–15 min at pH 8. Once bound, 45–100% of the metal ions were released from the sorbents after exposure to pH 3 buffer for 30 min. The transition metal ion loading capacity for the silk sorbents was considerably higher than that found for commercial ion exchange resins (AG MP-50 and AG 50W-X2) under similar conditions. Interestingly, total Cu2+ bound was found to be higher than theoretically predicted values based on known specific Cu2+ binding sites (AHGGYSGY), suggesting that additional (new) sites for transition metal ion binding sites are present in silk fibers. © 2011, Wiley-Blackwell.
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    Investigation of novel bis- and tris-tetraazamacrocycles for use in the copper-64 (Cu-64) radiolabeling of antibodies with potential to increase the therapeutic index for drug targeting
    (American Chemical Society, 2009-05) Ramli, M; Smith, SV; Lindoy, LF
    The 64Cu complexes of a series of mono-, bis-, and tris-tetraazamacrocycles have been prepared, and their stability in human sera has been assessed. The ligands forming the most stable Cu2+ complexes were then conjugated to the B72.3 antibody (mAb). Conditions for conjugation of the ligands to the mAb were optimized for the concentration of protein, ligand, pH, temperature, and time. The optimum moles of Cu2+ attached to the mAb were as high as 3.5 for L2 and 5.5 or 2.7 for L5, and the immunoreactivity was ≥80%. Biodistribution of the radioimmunoconjugates showed good tumor localization and target-to-background ratios that were significantly enhanced compared to those achieved with monotetraazamacrocyclic derivatives. © 2009, American Chemical Society
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    Layered double hydroxide nanoparticles incorporating terbium: applicability as a fluorescent probe and morphology modifier
    (Springer, 2010-01) Musumeci, AW; Xu, ZP; Smith, SV; Minchin, RF; Martin, DJ
    Stable and non-invasive fluorescent probes for nanotoxicological investigations are greatly needed to track the fate of nanoparticles in biological systems. The potential for terbium (Tb) to act as a fluorescent probe and its effect on layered double hydroxide (LDH) nanoparticle morphology are presented in this study. Incorporation of Tb during synthesis offers a simple methodology to easily tailor LDH nanoparticle thickness. A three-fold reduction in the average crystallite thickness (from 13 to 4 nm) has been achieved, whilst preferential lateral growth of LDH nanoparticles in the a-b crystal plane has been observed with increasing Tb loadings. Remarkably, Tb-LDH nanoparticles have emitted green fluorescence with a fluorescence quantum yield of 0.044. © 2010, Springer.
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    Metal ion binding properties of novel wool powders
    (Wiley-Blackwell, 2010-02-05) Naik, R; Wen, G; Dharmaprakash, MS; Hureau, S; Uedono, A; Wang, XG; Liu, XG; Cookson, PG; Smith, SV
    Wool fibres have shown potential for the removal and recovery of toxic chemical and metal ions; however, their slow kinetics of binding has limited their widespread application. In this study three wool powders have been prepared from chopped wool fibre using various milling operations. Brunauer, Emmett, Teller analysis (BET) showed negligible change in surface area and Positron annihilation lifetime spectroscopy indicated no change in nanoporosity of the powders on processing. Binding of the transition metal ions, Co2+, Cu2+, and Cd2+ was investigated over the pH range 3-9 at ambient temperature (23°C) using their respective radioisotopes (i.e. 57Co, 64Cu, or 109Cd). The optimum pH for binding of Cu2+ and Cd2+ was in the range 6-8, while Co2+ absorption peak was sharp at pH 8. The rate of uptake of Cu2+ for each of the wool powder was dramatically faster (42 fold) than that of the wool fibre. In comparison with commercial cation exchange resins, the wool powders showed significantly higher (two to nine fold) metal ion loading capacity. Selective binding of the metal ions could be enhanced by varying pH and/or incubation times. The use of radioisotopes to monitor the metal ion binding allowed the development of a highly sensitive and rapid high-throughput analysis method for assessing wool powder binding properties. The ability to produce large quantities of wool powders and their ease of handling indicate that they have potential for application in separation and recovery of metal ions from industrial effluents and environmental waterways. © 2010, Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.com
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    Molecular imaging with copper-64 in the drug discovery and development arena.
    (Informa Healthcare, 2007-05-01) Smith, SV
    The contribution of positron emission tomography (PET) to the drug discovery and development (D3) pipeline has been inhibited by the short half-lifes of PET radioisotopes, 11C and 18F, poor availability and the high cost of infrastructure. Copper-64 (64Cu) has a 12.7 h half-life, simple yet flexible radiochemistry and imaging characteristics that make it ideal for a wider application across the D3 arena. Recent scientific breakthroughs in the production of 64Cu show that it's, commercial production can be made more widely available. More importantly, for pharmaceutical research and development programmes wishing to incorporate the high sensitivity and spatial resolution of PET, but no desire to implement and maintain expensive radiochemistry infrastructure, 64Cu is an exciting option. © 2007, Informa Healthcare
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    Multiple patient batch production of 195mPt cisplatin and 195mPt carboplatin for use in drug risk assessment and optimisation of patient dose
    (Elsevier Science, 2010-08-01) Perkins, G; Smith, SV
    Platinum chemotherapeutics are used extensively as a first line treatment in over 28% of all cancers and widely as a second line treatment in combination with biological markers such as Herceptin. Over 20% of patients will experience maximum tolerate dose and significant side effects because dosage is often estimated using unreliable and indirect methods such as surface area and glomerular filtration rates. We are interested in providing a molecular imaging tool that allows the physician to screen a patient, monitor response and drug resistance and to personalise treatment regimes in order to reduce side effects. The ability to produce platinum radiopharmaceuticals commercially has been limited by long and unreliable synthetic processes. We have developed patent technology for the production of reactor base platinum radiopharmaceuticals, such as 195mPt-cisplatin and 195mPt-carboplatin. This study reports the neutron activation of 194platinum target material in the new research reactor OPAL and validation of the production of multiple (five) patient batches for both 195mcisplatin and 195mcarbplatin. Yields were 53±3% and 29±4%, respectively, with specific activities of up to 8MBq/mg. Production times were dramatically reduced from up to 24 h to less than 3 h using the new process.© 2010, Elsevier Ltd.
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    Nanocomposite bone cements for orthopaedic applications
    (Elsevier, 2010-06-06) Dunne, N; Ormsby, R; McNally, T; Mitchell, CA; Martin, DJ; Halley, PJ; Nicholson, T; Schiller, T; Gahan, LR; Musumeci, AW; Smith, SV
    Poly methylmethacrylate (PMMA) is the principal component of orthopaedic bone cement. However, it is susceptible to fatigue-related cracking or impact-induced failure. We have previously reported that adding MWCNTs (Multi Walled Carbon Nanotubes)(0.1wt.%) significantly improved the mechanical performance of PMMA-based bone cements and reduced the thermal necrosiscaused by the exothermic curing reaction of the cement [1].However, the effect of MWCNTs of various loading (wt.%) and functionality has yet to be considered. Recently there have been increased efforts to determine the effects of nanosized materials in vivo, with a particular emphasis on tracking their movement. Attachment of radioactive metal ions to MWCNTs via a bi-functional caged ligand would potentially allow for labelling and tracking. The objective of this study was to investigate the effect of MWCNT loading and functionality on mechanical, thermal and rheological properties of PMMA cements. In addition a method for radiolabelling MWCNTs has also been investigated Unfunctionalised, carboxyl (–COOH) functionalised and amine(–NH2) functionalised MWCNTs (Nanocyl S.A., Belgium) at varied wt% loadings (0.1, 0.25, 0.5, and 1.0) were incorporated into ColacrylB866 (Lucite International Ltd., UK) bone cement. Static mechanical properties were measured in accordance with ISO 5833:2002 [2].The plane strain fracture toughness was determined using Chevron-Notch Short Rod method [3]. The fatigue properties of the cements were determined in tension – tension with a lower stress of 0.3 MPa and an upper stress of 22.0 MPa being applied at a frequency of2 Hz [4]. Rheology was used to determine the time at which the onset of cure (tons) occurred and the critical gelation time (gel-time). Radioactive labelling of –COOH functionalised MWCNTs with gamma emitting 57Co (T1/2= 270 days) was completed using a bi-functional cage ligand (MeAMN3S3sar).Incorporating MWCNTs (≤0.25wt%) into cement significantly (p-value<0.001) improved the static and dynamic mechanical properties. However greater loadings of MWCNTs did not provide any further improvements and in some cases resulted in significant(p-value<0.001) reductions in mechanical properties. The extent of this effect was dictated by MWCNT functionality and the wt% used. Improvements were attributed to the MWCNTs arresting crack propagation. The exothermic polymerisation reaction for the PMMA cement was significantly reduced when thermally conductive MWCNTs were added. This was supported by the rheological characterisation as adding MWCNTs significantly altered tons and gel-time. The potential to radioactively label MWCNTs was successfully demonstrated, and further work will be conducted to assess the biological implications by tracking the radiolabelled MWCNTs under in vivo conditions. © 2006 Elsevier Ltd.
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    New 64Cu PET imaging agents for personalised medicine and drug development using the hexa-aza cage, SarAr.
    (Royal Society of Chemistry, 2006-09-07) Di Bartolo, N; Sargeson, AM; Smith, SV
    The success of positron emission tomography (PET) in personalised medicine and drug development requires radioisotopes that provide high quality images and flexible chemistry for a broad application. 64Cu is arguably one of the most suitable PET isotopes for imaging with the evolving target agents, but there are not many appropriate chelating agents for 64Cu and this has limited its wider application. The bi-functional chelator, SarAr is known to bind 64Cu2+ quantitatively (i.e. one metal per ligand present) and rapidly (<2 min) at 10−6 M over a range of pH (4–9). In this paper the conjugation of SarAr to the whole and fragmented antibody is described. Conjugation of the SarAr to the protein does not impair its coordination of the 64Cu. It complexes the 64Cu2+ rapidly, quantitatively and essentially irreversibly at pH 5. Animal studies show that the 64Cu–SarAr–immunoconjugates maintain their specificity for the target and are stable in vivo. Also, SarAr is a platform technology, is easy to use in a kit formulation and is readily adaptable for the wider application in 64Cu PET imaging. © 2006, Royal Society of Chemistry
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    Optimizing radiolabeling amine-functionalized silica nanoparticles using SarAr-NCS for applications in imaging and radiotherapy
    (American Chemical Society, 2013-05-07) Kong, L; Mume, E; Triani, G; Smith, SV
    Silica nanoparticles functionalized with amine groups and in the size range of approximately 60–94 nm were produced by combining sol–gel processing and emulsion technology. Hexa-aza cage ligand SarAr-NCS was conjugated to the silica nanoparticles and subsequently radiolabeled with a solution of 57Co2+-doped carrier Co2+. The number of Co2+ ions bound to the silica particles at pH 7 was used to determine the average number of available SarAr-NCS ligands conjugated to a silica particle. For organically modified silica particles of 94.0 and 59.5 nm diameter, the maximum number of metal binding sites was determined to be 11700 and 3270 sites per particle, respectively. For silica particles (63.5 nm peak diameter) produced using an water-in-oil emulsion, the calculated average was 4480 on the particle surface. The number of SarAr-NCS conjugated on the particles was easily controlled, potentially providing for a range of products for applications in the risk assessment of particles and theranostic imaging or radiotherapy when radiolabeled with a suitable radioisotope such as 64Cu or 67Cu. © 2013, American Chemical Society.
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    Positron emission tomography (PET) imaging of neuroblastoma and melanoma with 64Cu-SarAr immunoconjugates
    (National Academy of Sciences, 2007-10-30) Voss, SD; Smith, SV; DiBartolo, N; McIntosh, LJ; Cyr, EM; Bonab, AA; Dearling, JLJ; Carter, EA; Fischman, AJ; Treves, ST; Gillies, SD; Sargeson, AM; Huston, JS; Packard, AB
    The advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement 18F-FDG. Copper-64 (64Cu) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high in vivo lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1-N-(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.6.6] eicosane-1,8-diamine) for use in developing a new class of tumor-specific 64Cu radiopharmaceuticals for imaging neuroblastoma and melanoma. The anti-GD2 monoclonal antibody (mAb) 14.G2a, and its chimeric derivative, ch14.18, target disialogangliosides that are overexpressed on neuroblastoma and melanoma. Both mAbs were conjugated to SarAr using carbodiimide coupling. Radiolabeling with 64Cu resulted in >95% of the 64Cu being chelated by the immunoconjugate. Specific activities of at least 10 μCi/μg (1 Ci = 37 GBq) were routinely achieved, and no additional purification was required after 64Cu labeling. Solid-phase radioimmunoassays and intact cell-binding assays confirmed retention of bioactivity. Biodistribution studies in athymic nude mice bearing s.c. neuroblastoma (IMR-6, NMB-7) and melanoma (M21) xenografts showed that 15–20% of the injected dose per gram accumulated in the tumor at 24 hours after injection, and only 5–10% of the injected dose accumulated in the liver, a lower value than typically seen with other chelators. Uptake by a GD2-negative tumor xenograft was significantly lower (<5% injected dose per gram). MicroPET imaging confirmed significant uptake of the tracer in GD-2-positive tumors, with minimal uptake in GD-2-negative tumors and nontarget tissues such as liver. The 64Cu-SarAr-mAb system described here is potentially applicable to 64Cu-PET imaging with a broad range of antibody or peptide-based imaging agents. © 2007, National Academy of Sciences