Browsing by Author "Oehlke, E"

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    Developing national capability for the production and use of radiometal based radiopharmaceuticals
    (John Wiley & Sons, Inc, 2013-04-11) Lengkeek, NA; Pellegrini, PA; Oehlke, E; Fraser, BH; Greguric, I
    Radiometals remain key radioisotopes for radio-medicine; the mainstay diagnostic medical imaging isotope, 99mTc, and important radioisotopes for radiotherapy, 90Y and 153Sm. However, the worldwide growth in PET centres, driven by the wildly successful [18F]-FDG, has provided a yet to be seized opportunity to deliver radiometal-based radiopharmaceuticals with clinical relevance to researchers. An ever growing set of radiometals is becoming available in Australia covering a wide range of half-lives, nuclear and chemical properties, these include 64Cu, 68Ga, 86Y, 89Zr, and looking into the near future, 44Sc, 45Ti and 90Nb. ANSTO's Lifesciences division is working to provide the Australian academic and clinical communities access to the following key areas. Radioisotope supply Two in-house 68Ge/68Ga generators; one solely for research and a larger generator for pre-clinical trials, provide access to this key radioisotope. ANSTO has provided financial and technical support to numerous cyclotron centres around Australia for development of solid targetry facilities, ensuring supply of 124I, 64Cu, 86Y and 89Zr in the short-term and 44Sc, 45Ti and 90Nb later. In coming years the OPAL reactor will begin producing pharmaceutical grade 177Lu as part of the Australian government's investment in nuclear medicine. Radiometal Labelling Research and Development In addition to our programs developing new ligands, tracers and improved radiometal labelling procedures, Lifesciences is supporting the development of new biomolecule treatments by providing researchers access to laboratories, procedures and expertise tailored specifically for functionalising biomolecules for radiometal labelling. Preclinical Radiometal Tracer Development We are working to deliver novel radiometal-based diagnostic tracers to the Australian research and clinical community by accessing the pre-clinical programs of our key international partnerships at Memorial Sloan Kettering Cancer Centre and Massachusetts General Hospital. Our initial objective is to supply the antibodies, i.e. [ 89 Zr]-J591. As our supply radiometals is diversified we will expand into proteins, peptides and other biomolecules. © 2013 John Wiley & Sons, Inc.
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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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    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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    Synthesis and radiolabelling of DOTA-linked glutamine analogues with 67,68Ga as markers for increased glutamine metabolism in tumour cells
    (MDPI (Multidisciplinary Digital Publishing Institute), 2013-06-19) Pellegrini, PA; Howell, NR; Shepherd, R; Lengkeek, NA; Oehlke, E; Katsifis, A; Greguric, I
    DOTA-linked glutamine analogues with a C6- alkyl and polyethyleneglycol (PEG) chain between the chelating group and the l-glutamine moiety were synthesised and labelled with 67,68Ga using established methods. High yields were achieved for the radiolabelling of the molecules with both radionuclides (>90%), although conversion of the commercially available 67Ga-citrate to the chloride species was a requirement for consistent high radiochemical yields. The generator produced 68Ga was in the [68Ga(OH)4]− form. The 67Ga complexes and the 67Ga complexes were demonstrated to be stable in PBS buffer for a week. Uptake studies were performed with longer lived 67Ga analogues against four tumour cell lines, as well as uptake inhibition studies against l-glutamine, and two known amino acid transporter inhibitors. Marginal uptake was exhibited in the PEG variant radio-complex, and inhibition studies indicate this uptake is via a non-targeted amino acid pathway. © 2013 by the authors