Neorx Corporation

University of Missouri

Other

Bristol-myers Squibb Pharma Company

Fu-Min Su

Jean-Luc VanderHeyden

Alan R Fritzberg

Gary J Ehrhardt

Prasanna Venkatesan

Joseph E Bugaj

John M Reno

Linda M Gustavson

Louis J Theodore

Robert E Lewis

Jean-Luc E Vanderheyden

Keith R Olewine

Peter S Holton

Timothy A Lane

Jean-Luc E Vanderhevden

Methods and apparatus for separating ions of metallic elements are provided. Preferred methods utilize a hydrophobic chelating extractant, such as an organophosphorus compound, adsorbed onto carbon or graphite fibers in the form of felt. Also described is a new thallium-201 generator that comprises a column containing an acidic organophosphorus extractant adsorbed on carbon or graphite fibers, and a yttrium-90 generator system comprised of two extraction columns designed to selectively absorb yttrium-90 at different pH, to enable the separation of yttrium-90 from strontium-90. The two columns are connected in series for stepwise separation. The yttrium-90 product is freed from residual strontium-90 and metal contaminants and can be eluted from the second column with dilute acid, acetate buffer, water or saline for labeling biological targeted molecules. The new generator system provides rapid and efficient separation of yttrium-90 and is amenable to both scale-up and automation. Also described is a newTc generator that comprises a column containing an acidic organophosphorus extractant adsorbed on carbon or graphite fibers designed to selectively absorbMo at a selected pH, to enable the separation ofTc fromMo.

Method and apparatus for separating ions of metallic elements in aqueous solution

Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin, as well as related compounds, are described. Articles of manufacture useful in pretargeting methods are also discussed.

Pretargeting methods and compounds

Stable therapeutic radionuclide compositions comprising, for example, .sup.186 Re, .sup.188 Re and .sup.131 I stably bound to a proteinaceous targeting moiety and suitable for human in vivo administration are disclosed. Stabilizing agents preferably comprise antioxidants and challenging agents, and combination of HSA with an antioxidant and/or challenging agent provides enhanced long term stability. Ascorbic acid is an especially preferred stabilizing agent, which provides stability of therapeutic radionuclide compositions at levels of at least about 90% for several hours up to several days.

Stable therapeutic radionuclide compositions and methods for preparation

Water soluble irradiation targets are disclosed for the production of .sup.186 Re and .sup.188 Re. The irradiation targets are selected for both water solubility and absence of elements which would produce contaminating isotopes for medical therapeutic and diagnostic use. In one embodiment, .sup.186 Re or 188Re is produced by the direct irradiation of a water soluble irradiation target comprising .sup.185 Re or .sup.187 Re, respectively. Preferred targets for this purpose include aluminum perrhenate, lithium perrhenate and magnesium perrhenate. In another embodiment, a zirconyl tungstate generator comprising .sup.188 W for the production of .sup.188 Re is obtained by irradiating a soluble irradiation target comprising .sup.186 W, dissolving the irradiated target in aqueous solution, reacting the dissolved target with an aqueous solution comprising zirconyl ion to form an insoluble zirconium tungstate precipitate and disposing the precipitate in an elutable container. Preferred irradiation targets for this purpose include sodium tungstate and lithium tungstate. In each of the foregoing embodiments, the irradiation target is readily soluble in aqueous solution and may be used directly in solution form after irradiation, such as for ligand conjunction for medical diagnostic or therapeutic purposes, without cumbersome dissolution, neutralization, purification and other processing steps involving irradiated materials inherent in prior .sup.186 Re and .sup.188 Re production methods.

Soluble irradiation targets and methods for the production of

Water soluble irradiation targets are disclosed for the production of .sup.186 Re and .sup.188 Re. The irradiation targets are selected for both water solubility and absence of elements which would produce contaminating isotopes for medical therapeutic and diagnostic use. In one embodiment, .sup.186 Re or .sup.188 Re is produced by the direct irradiation of a water soluble irradiation target comprising .sup.185 Re or .sup.187 Re, respectively. Preferred targets for this purpose include aluminum perrhenate, lithium perrhenate and magnesium perrhenate. In another embodiment, a zirconyl tungstate generator comprising .sup.188 W for the production of .sup.186 Re is obtained by irradiating a soluble irradiation target comprising .sup.186 W, dissolving the irradiated target in aqueous solution, reacting the dissolved target with an aqueous solution comprising zirconyl ion to form an insoluble zirconium tungstate precipitate and disposing the precipitate in an elutable container. Preferred irradiation targets for this purpose include sodium tungstate and lithium tungstate. In each of the foregoing embodiments, the irradiation target is readily soluble in aqueous solution and may be used directly in solution form after irradiation, such as for ligand conjunction for medical diagnostic or therapeutic purposes, without cumbersome dissolution, neutralization, purification and other processing steps involving irradiated materials inherent in prior .sup.186 Re and .sup.188 Re production methods.

Improved radionuclide generators include a substantially insoluble salt of a parent radionuclide precursor which may be directly irradiated and then packed in a column for subsequent elution of the daughter radionuclide without the production of counter ion isotopic contaminants. The parent radionuclide precursor is provided in the form of an insoluble salt of the parent element whose counter ion, preferably aluminum, forms a relatively soluble salt with the desired daughter radionuclide. The improved generators may be prepared by reacting a parent radionuclide precursor with aluminum to obtain an aluminum salt of the precursor having low solubility in water, irradiating the aluminum salt to obtain an irradiated aluminum salt of the parent radionuclide, and then disposing the irradiated parent radionuclide in an elutable container. Useful parent radionuclide precursors include molybdenum-98 in the form of molybdate for the production of daughter .sup.99m Tc, as soluble pertechnetate, and tungsten-186 in the form of tungstate for the production of daughter .sup.188 Re as soluble perrhenate. The daughter .sup.99m Tc or .sup.188 Re may be eluting the generator matrix, e.g., with a saline solution.

Radionuclide generator system and method for its preparation and use

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Seattle, WA, United States of America

Fu-Min Su