Browsing by Author "Le, VS"

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    Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation Part I. Multi-column chromatographic process for clinically applicable
    (Springer, 2008-09-01) Le, VS; Morcos, N; Zaw, M; Pellegrini, PA; Greguric, I
    The conventional multi-column solid phase extraction (SPE) chromatography technique using di-(2-ethylhexyl)orthophosphoric acid (HDEHP) impregnated OASIS-HLB sorbent based SPE resins (OASIS-HDEHP) was developed for the separation of no-carrier added (n.c.a) Lu-177 from the bulk quantity of ytterbium target. This technique exploited the large variation of lutetium metal ion distribution coefficients in the varying acidity of the HCl solution-OASIS-HDEHP resin systems for the consecutive loading-eluting cycles performed on different columns. The production batches of several hundred mCi n.c.a Lu-177 radioisotope separated from 50 mg Yb target activated in a nuclear reactor of medium neutron nux (Phi = 5 center dot 10(13) n.cm(-2).s(-1)) were successfully performed using the above mentioned separation technique. With the target irradiation in a reactor of thermal neutron flux Phi = 2 center dot 10(14) n.cm(-2).s(-1) or the parallel run of several separation units, many Ci-s of n.c.a Lu-177 can be profitably produced. The OASIS-HDEHP resin based multi-column SPE chromatography technique makes the separation process simple and economic and offers an automation capability for operation in highly radioactive hazardous environments. © 2008, Springer.
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    Alternative method for Cu-64 radioisotope production
    (Elsevier, 2008-05-12) Le, VS; Howse, J; Zaw, M; Pellegrini, PA; Katsifis, A; Greguric, I; Weiner, R
    The method for 64Cu production based on a 64Ni target using an 18 MeV proton energy beam was developed. The studies on the optimisation of targetry for the 18 MeV proton bombardments were performed in terms of the cost-effective target utilisation and purity of the 64Cu product. The thickness-specific 64Cu yield (μCi/(μA×μm)) was introduced into the optimisation calculation with respect to cost-effective target utilisation. A maximum target utilisation efficacy factor (TUE) was found for the proton energy range of 2.5–13 MeV with corresponding target thickness of 36.2 μm. With the optimised target thickness and proton energy range, the 64Ni target thickness saving of 45.6% was achieved, while the overall 64Cu yield loss is only 23.9%, compared to the use of the whole effective proton energy range of 0–18 MeV with target thickness of 66.6 μm. This optimisation has the advantage of reducing the target amount to a reasonable level, and therefore the cost of the expensive 64Ni target material. The 64Ni target electroplated on the Au–Tl multi layer coated Cu-substrate was a new and competent design for an economic production of high quality 64Cu radioisotope using an 18 MeV proton energy cyclotron or a 30 MeV cyclotron with proton beam adjustable to 18 MeV. In this design, the Au coating layer plays a role of protection of “cold” Cu leakage from the Cu substrate and Tl serves to depress the proton beam energy (from 18 MeV to the energy optimised value 13 MeV). The ion exchange chromatographic technique with a gradient elution was applied to improve the 64Cu separation with respect to reducing the processing time and control of 64Cu product quality. © 2009, Elsevier Ltd.
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    Chemical synthesis and application of zirconium and titanium polymer compounds for the preparation of Tc-99m and Re-188 chromtographic generators
    (IAEA’S coordinated research project 2nd research coordination meeting, 2006-04-03) Le, VS
    PZC adsorbent for the preparation of PZC based chromatographic Tc-99m and / or Re-188 generators was successfully synthesized and its chemical composition, molecular structure was determined. 99Mo and/or 188W -adsorption on PZC in different solutions and 99mTc and/or 188Re elution from PZC columns were investigated. Mo- adsorption capacity of about 285 mgMo/gPZC and Tc-99m elution yield of higher than 90% were achieved with PZC adsorbent. Mo-99 breakthrough of 0.015% and Molybdenum element breakthrough of lower than 5μg Mo/ml were found in Tc-99m eluate. W- adsorption capacity of about 520 mgW/gPZC and Re-188 elution yield of higher than 80% were also achieved with PZC adsorbent. W-188 breakthrough of 0.015% and Tungsten element breakthrough of lower than 5 μg W /ml were found in Tc-99m eluate. A good relationship between the W- or Mo-content of adsorption solution and the adsorption capacity, adsorption percentage, chemical breakthrough and relevant radionuclide elution yield was found.
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    Development of 68Ga generator at ANSTO
    (Medknow Publications, 2011-06-23) Le, VS; Izard, M; Pellegrini, PA; Zaw, M
    A 68 Ge/ 68 Ga generator combined with automated 68 Ga eluate purification unit was developed to produce 68 Ga solution suitable for labelling peptide ligands for PET radiopharmaceutical applications. The sorbent of a Ti-Zr ceramic structure [1] was used as a generator column packing material. 68 Ga eluate of around 5 mL volume in 0.1 M HCl solution was purified on a small cation exchanger column with an aqueous alcohol solution mixture of hydrochloric acid, ascorbic acids and halide salts. An alkali solution was used for elution of 68 Ga from the ion exchange resin column to obtain a purified 68 Ga solution which is conditioned with acidic solutions to obtain a final 68 Ga product of pH=3-4 in 0.75 mL 0.5 M NaCl or 0.5 M sodium acetate solution. The organic solvent free 68 Ga solution product of acidity suitable for coordination chemistry based labelling of the peptide ligands was successfully used for preparation of DOTATATE and DOTATOC PET radiopharmaceuticals. The process of 68 Ga elution from the generator followed by 68 Ga eluate purification was performed using a low-cost automation bench-top system. [2] This system is designed based on the timing sequence of seven processing steps without feedback control. The variable flow rate of eluents used for elution/purification in this system also ensure the optimisation of operating times with respect to different adsorption/ desorption kinetics of 68 Ga ion species, which is controlled by the sorbent and ion exchange resin used in the generator and purification columns. © 2011, Medknow publication
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    Development of a titanium tungstate-based 188W/188Re gel generator using tungsten of natural isotopic abundance
    (Elsevier Science Ltd, 2002-11-01) Dadachov, MS; Le, VS; Lambrecht, RM; Dadachova, E
    The feasibility of developing titanium tungstate-based 188W/188Re gel generator using tungsten of natural isotopic abundance irradiated in a moderate flux reactor has been investigated. Influence of temperature, pH and eluent concentration on generator performance was studied. It was found that ‘‘post-formed’’ approach allows to construct gel generators with elution performance and 188Re elution yields very close to those of conventional alumina 188W/188Re generator. Curie-level 185W radionuclidic impurity presents a challenge during the processing of target material and subsequent elution of the generator. In the future use of semi-enriched with 186W target material (50–60% enrichment) would be beneficial in the development of titanium tungstate-based 188W/188Re gel generators. 2002 Elsevier Science Ltd.
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    Development of alternative technologies for a gel-type chromatographic Tc-99m generator
    (Wiley-Blackwell, 1994-04-01) Le, VS; Lambrecht, RM
    There is continuing concern worldwide about the need for multiple sources of the 99Mo generator, and the large investment required to introduce the use of 235U (n, f) 99Mo derived production at a mew facility. This is sufficient justification required for research on the development of technologies for a gel-type chromatographic 99mTc generator based on the 98Mo(n,r)99 Mo nuclear reaction. The synthesis of Titanium-Molybdate (abbrev. TiMo) generator packing gel pre-formed for 98Mo(n,r)99 Mo neutron activation of TiMo; and Zirconium-Molybdate (abbrev. ZrMo) gel columns containing (n,r) produced 99Mo for preparation of chromatographic 98mTc generators was studied. The chemistry of polymerisation, and amorphous or crystalline TiMo and ZrMo formating of the molybdate polyanion was investigated for the interpretation of the 99mTc-elution performance from the gel generators. Preparatory conditions of TiMo and ZrMo were found to be very critical. The complexity in the preparation of TiMo and ZrMo is attributed to the large capability of polymeric hydroxl complexes of Ti+4 and Zr+4 ions in the aqueous solution. The preparation of TiMo and ZrMo requires a process of high standardisation to give a product of consistent quality. X-ray diffraction patterns of the MoTi gel were similar between batches. Behaviours, such as target temperature, irradiation stability, and neutron self-shielding, of the TiMo gel under reactor irradiation conditions that effect the performance of the generator and the quality of the 99mTc pertechnetate elucate were measured. The specifications of TiMo and ZiMo gel columns of high 99mTc elution performance, and chromatographic 99mTc generator options yielding 99mTc fulfilling the requirements for nuclear medicine applications with several conventional kits will be illustratively described. The eluents used in the generator options are saline, redistilled water, or even organic solvent such as acetone, MEK. Fifty gel generators this type were tested in different hospitals in Vietnam, and gave satifactory results. The gel generator concept is particularly relevant to hospitals in developing countries that do not have access to fission produced 99Mo generators. Also a satisfactory gel-type generator based on (n,r)99 Mo Should be economical to produce. © 1994, Wiley-Blackwell
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    Influence of metal ions on the Ga-68-labeling of dotatate
    (Elsevier, 2013-12-01) Oehlke, E; Le, VS; Lengkeek, NA; Pellegrini, PA; Jackson, TW; Greguric, I; Weiner, R
    The influence of metal cations (Fe3+, Fe2+, In3+, Cu2+, Ca2+, Al3+, Co2+, Lu3+, Ni2+, Pb2+, Ti4+, Y3+, Yb3+, Zn2+, and Zr4+) on the radiolabeling yield of [68Ga(DOTATATE)] was evaluated. Our most important observation was that, within our experimental limit, the metal ion/ligand ratio plays a critical role on the influence of most metal ions. More in-depth studies, with Cu2+ and Fe3+, revealed that reaction temperature and concentration changes have little effect, but speciation changes with pH are crucial. Furthermore, we found that [68Ga(DOTATATE)] is stable in the presence of high concentrations of Fe3+, Zn2+ and Pb2+, but transmetalates with Cu2+ at 95 °C. © 2013, Elsevier Ltd.
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    New SPE column packing material: Retention assessment method and its application for the radionuclide chromatographic separation
    (Springer, 2008-03-01) Le, VS; Morcos, N
    The preparation of the OASIS®-HLB sorbent based solid phase extraction (SPE) resins and their application for the 177Lu radioisotope separation were investigated. Di-(2-ethylhexyl) orthophosphoric acid (HDEHP) impregnated OASIS-HLB sorbent based SPE resins (OASIS-HDEHP) were successfully developed from this investigation. The wettable porosity structure of the moderately extractant impregnated OASIS-HDEHP resins is favorable for the effective diffusion of polar and ionic solutes giving good separation performance. Its good wetting ability offers ease of packing into conventional chromatographic columns. Their off-gassing-free operation makes OASIS-HDEHP columns good for long term use with highly consistent elution dynamics (several dozens of separations perfectly achievable on the same column). The simple method for the capacity factor (k’) evaluation was developed to facilitate the characterization of the SPE chromatographic resin column. A competent procedure using OASISE30RS resin (one member of the OASIS-HDEHP resin group) for the separation of no-carrier added (n.c.a) 177Lu from the bulk amount of Yb target was developed. This separation procedure has showed very good performance with several prominent advantages such as the much shorter separation time (5–6 hours) and high reproducibility. Its high adsorption capacity for Yb and Lu makes it ideal for the separation of the bulky sample (50 mg Yb target for the 20 g weight resin column) for the production of the several Ci of 177Lu radioactivity. © 2008, Springer.
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    Polymeric titanium oxychloride sorbent for 188W/188Re nuclide pair separation
    (Taylor & Francis, 2009-01) Le, VS; Nguyen, CD; Pellegrini, PA; Bui, VC
    The chemical synthesis conditions (TiCl4: iPrOH reagent ratio and reaction temperature scheme) were optimized for the preparation of polymeric titanium oxychloride sorbent which met the requirements for clinically useful 188W/188Re generator production, such as high W-adsorption capacity, high 188Re-elution yield, low 188W-breakthrough, and good mechanical stability. This polymeric material was formed by polycondensation of titanium-oxychloride units, the chemical formula of which was supposed as [OTiO (Ti40 Cl80 (OH) 80 (TiO2)95.60H2O) OTiO]n. The effect of the W-content of tungstate solution on the WO42- ion adsorption (with minimizing the poly-tungstate ion adsorption) and its covalent bonding with the Ti metal atoms in the polymeric matrix were justified with respect to the optimal W-adsorption conditions for the preparation of a useful 188W/188Re generator column. The high W-adsorption capacity of about 515.6 mg W/g sorbent and 188Re elution yield of higher than 85% wereachieved. The large difference in the distribution ratio values found for alumina and polymeric titanium oxychloride sorbent in 0.005% NaCl solution (DW,Re-188 = 50 and DW, Re-188 = 1.0, respectively) offered an advantage for the preparation of a consecutive-elution based 188Re generator system which combined both 188Re elution and 188Re concentrating processes in one portable system. This generator system is of a tandem column type which consists of a polymeric titanium oxychloride sorbent coupled to an alumina column. This system gave a 188Re concentration factor of approximately 10. The overall 188Re yield achieved from this system was >80%. 188W isotope and elemental tungsten breakthrough were not detected in its 188Re eluate. This system thus offers a potential application for clinically useful 188Re production using low specific radioactivity 188W (around 500 mCi/g) producible in a medium neutron flux reactor. © 2009, Taylor & Francis Ltd.
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    Preparation of inorganic polymer sorbents and their application in radionuclide generator technology
    (International Atomic Energy Agency, 2009-07-01) Le, VS; Nguyen, CD; Bui, VC; Vo, CH
    Absorbents based on poly zirconium compound (PZC) and poly titanium compound (PTC) were synthesized for the preparation of 188W/188Re generators. The chemical composition, molecular structure and physicochemical characteristics of these adsorbents were investigated. The adsorption properties of PZC and PTC sorbents in different tungstate solutions and the elution performance were investigated. Tungsten adsorption capacities of about 520 mg of tungsten per gram of PZC and 515 mg of tungsten per gram of PTC and a 188Re elution yield greater than 80% for both PZC and PTC sorbents were achieved. A 188Re eluate concentration process was developed by eluting 188Re from the tandem system of 188W-PTC-alumina columns with two different concentrations of saline solution, which gave a concentration factor of about 6. The technology developed can be used for the preparation of clinically applicable 188W/188Re generators using low specfic radioactivity 188W produced in medium flux research reactors. Copyright 2009 © IAEA. All rights reserved
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    Preparation of PZC based 99m TC generator to be available for clinic for clinical application
    (IAEA’s coordinated research project first research coordination meeting, 2004-10-04) Le, VS
    The performance of PZC was investigated for chromatographic Tc-99m generator preparation. Mo-adsorption of PZC in different Mo-solutions and Tc-99m elution of 99Mo-PZC column were studied. Mo- adsorption capacity of higher than 250mgMo/gPZC and Tc-99m elution yield of higher than 80% were achieved with PZC adsorbent. Mo-99 breakthrough of 0.02% and Molybdenum element breakthrough of around 5µg Mo/ml were found in Tc-99m eluate. A good relationship between the Mo-content of adsorption solution and the Mo-adsorption capacity, adsorption percentage, Mo-breakthrough and Tc-99m elution yield was found. The column pre-loading procedure for the preparation of PZC based chromatographic Tc-99m generators were described in detail .
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    Radiochemical separation and quality assessment for the 68Zn target based 64Cu radioisotope production
    (Springer, 2008-08-01) Le, VS; Pellegrini, PA; Katsifis, A; Howse, J; Greguric, I
    The radiochemical separation of the different radionuclides (64Cu, 67Cu, 67Ga, 66Ga, 56Ni, 57Ni, 55Co, 56Co, 57Co, 65Zn, 196Au ) induced in the Ni supported Cu substrate – 68Zn target system, which was bombarded with the 29.0 MeV proton beam, was performed by ion-exchange chromatography using successive isocratic and/or concentration gradient elution techniques. The overlapped gamma-ray spectrum analysis method was developed to assess the 67Ga and 67Cu content in the 64Cu product and even in the post-67Ga production 68Zn target solution without the support of radiochemical separation. This method was used for the assessment of 64+67Cu radioisotope separation from 67Ga , the quality control of 64Cu product and the determination of the 68Zn (p,2p)67Cu reaction yield. The improvement in the targetry and the optimization of proton beam energy for the 68Zn target based 64Cu and 67Ga production were proposed based on the stopping power and range of the incident proton and on the excitation functions, reaction yields and different radionuclides induced in the target system. © 2008, Springer.
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    The role of additives in moderating the influence of Fe(III) and Cu(II) on the radiochemical yield of [68Ga(DOTATATE)]
    (Elsevier B.V., 2016-01) Oehlke, E; Lengkeek, AL; Le, VS; Pellegrini, PA; Greguric, I; Weiner, R
    68Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe3+ and Cu2+, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [68Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe3+ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu2+ and Fe3+ to Cu+ and Fe2+ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3+ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe3+ (0.25 mM) and 100 nmol Cu2+ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3. © 2015 Elsevier B.V.
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    Specific radioactivity of neutron induced radioisotopes: assessment methods and application for medically useful 177Lu production as a case
    (MDPI Publishing, 2011-01-01) Le, VS
    The conventional reaction yield evaluation for radioisotope production is not sufficient to set up the optimal conditions for producing radionuclide products of the desired radiochemical quality. Alternatively, the specific radioactivity (SA) assessment, dealing with the relationship between the affecting factors and the inherent properties of the target and impurities, offers a way to optimally perform the irradiation for production of the best quality radioisotopes for various applications, especially for targeting radiopharmaceutical preparation. Neutron-capture characteristics, target impurity, side nuclear reactions, target burn-up and post-irradiation processing/cooling time are the main parameters affecting the SA of the radioisotope product. These parameters have been incorporated into the format of mathematical equations for the reaction yield and SA assessment. As a method demonstration, the SA assessment of 177Lu produced based on two different reactions, 176Lu (n,γ)177Lu and 176Yb (n,γ) 177Yb (β- decay) 177Lu, were performed. The irradiation time required for achieving a maximum yield and maximum SA value was evaluated for production based on the 176Lu (n,γ)177Lu reaction. The effect of several factors (such as elemental Lu and isotopic impurities) on the 177Lu SA degradation was evaluated for production based on the 176Yb (n,γ) 177Yb (β- decay) 177Lu reaction. The method of SA assessment of a mixture of several radioactive sources was developed for the radioisotope produced in a reactor from different targets. © 2011, MDPI Publishing
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    Synthesis, characterization and application of zirconium and titanium inorganic polymer sorbents for the preparation of chromatographic 99mTc and 188Re generators
    (IAEA’s coordinated research project 3rd research coordination meeting, 2007-10-08) Le, VS
    The Zirconium polymer compound (PZC) and Titanium polymer compound (PTC) based adsorbents for the preparation of chromatographic 99mTc and 188Re generators were synthesized. Chemical composition, molecular structure and physicochemical characteristics of these adsorbents were investigated. The adsorption propertiies of PZC and PTC sorbents in the different Molybdate and Tungstate solutions and the daughter nuclide elution performance were investigated. The Molybdenum adsorption capacities of about 275 mgMo/gPZC and 270 mgMo/gPTC and the 99mTc elution yield higher than 90% were achieved with both sorbents. The 99Mo breakthrough of 0.015% and Molybdenum element breakthrough lower than 2μg Mo/ml were found in the 99mTc eluate. The Tungsten adsorption capacities of about 520mgW/gPZC and 515 mgW/gPTC and the 188Re elution yield higher than 80% were also achieved with both PZC and PTC sorbents. The 188W breakthrough of 0.015% and Tungsten element breakthrough lower than 5 μg W /ml were found in the 188Re eluate.The parent nuclide adsorption capacity and the daughter nuclide elution performance of PTC sorbent resembled closely that of PZC one, except that the breakthrough of 99Mo and 188W parent nuclides was higher and PTC column needed smaller saline volume to elute 99mTc and 188Re daughter nuclides. The188Re eluate concentration process was developed by eluting 188Re from the tandem system of 188W-PTC – Alumina columns with the different concentration saline solutions. The concentration factor higher than 6 was achieved by this concentration technique which offered a potential application for the clinically applicable 188W-188Re generator production using low specific radioactivity 188W produced in rather low power research reactors.
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    Theoretical assessment of specific radioactivity: the effect of target burn-up, isotope dilution and target purity and the application for 177Lu production
    (Asia-Pacific Symposium on Radiochemistry '09, 2009-11-29) Le, VS
    The wide expansion of targeting radiotherapy depends a lot on the availability of metallic radionuclide with high specific radioactivity (SA). As an example, as high as 20 Ci / mg SA of 177Lu is required to formulate the targeting radiopharmaceuticals for different cancer treatments. High SA nuclide can be produced using a neutron capture reaction of the target nuclide of high cross section (such as 176Lu (n, gamma) 177Lu, б = 2300 b). This direct route could be successfully performed in the nuclear reactor of rather high neutron flux which is accessible in only a handful of countries in the world. However, large burn-up of the target nuclide during high neutron flux irradiation may cause a problem of degrading the SA value of the produced nuclide if the target contains isotopic impurities. No-carrier- added (n.c.a) radioisotopes can be produced via a process of neutron capture-followed-by-beta particle decay (such as 176Yb (n, gamma) 177Yb ( β- decay) 177Lu). In this case, the same reduction in SA was also experienced if the target contains the isotopic and/or elemental impurities, one radionuclide of which is expected to be produced. The 177Lu production was reported in many publications 1-3, but until now the product quality assessment, especially the evaluation of 177Lu specific radioactivity in the product is not sufficiently performed. The SA assessment was based on the calculation of nuclear reaction and radioactive transformation yield as a function of thermal neutron flux, target nuclide burn-up, isotopic composition and irradiation and post-activation processing time. Among the factors affecting SA the target composition (elemental and isotopic impurities), target nuclide burn-up and the irradiation and processing time are most accounted for. Theoretical SA assessment has definitely given us a firm ground to set up an optimized process for the production of clinically applicable radioactive product. The specific radioactivity of radionuclide formed via neutron capture followed by radioactive transformation and its application for 177Lu production using indirect route 176Yb (n, gamma) 177Yb (β - decay) 177Lu was evaluated. In contrast to the direct route involving the 176Lu (n, gamma) 177Lu reaction, the indirect production route of 177Lu using 176Yb enriched target gives a product of high SA. However, the product is never carrier free due to the elemental Lu and isotopic 174Yb impurities in the 176Yb enriched target. 175Lu isotope generated from 174Yb (n, gamma) 175Yb (β - decay) 175Lu process and elemental Lu impurities remaining in the 177Lu product (which is chemically separated from 176Yb target) makes the 177Lu SA value strongly decreased. Based on the above mentioned assessment method the effect of several factors (such as elemental Lu impurity, isotopic 174Yb content and isotope dilution) on the 177Lu SA degradation was evaluated. As a result obtained, the specific radioactivity of n.c.a 177Lu produced from 176Yb target was strongly affected by irradiation time and impurities of the target. The production yield and desired specific activity should be compromised to achieve a cost effective production of clinically applicable 177Lu product. The experimental results reported in our previous publications have well agreed with theoretical calculation results.