University of Missouri

Neorx Corporation

Mallinckrodt Medical, Inc.

Gary J Ehrhardt

Delbert E Day

Fu-Min Su

Kurt R Zinn

Wei Jia

Edward A Deutsch

Robert G Wolfangel

Cathy Sue Cutler

Hendrik Petrus Engelbrecht

Jean-Luc E Vanderheyden

Steven Symes

Robert K Guimon

Jean-Luc E Vanderhevden

The present invention provides a simple and inexpensive method for removing metal and other impurities in a radioisotope solution. The invention further includes the development of a new parent/daughter generator system for collecting the daughter isotope in a concentrated solution.

Method and system for purifying charged radioisotopes

Methods for the production of radionuclides suitable for use in radiopharmaceuticals for diagnostic and therapeutic applications, and specifically, to the production of,Re,,Re and other radionuclides such as,Pt and,Au using an inorganic Szilard-Chalmers reaction. Thin-film and powdered,Re,metal targets, and,Re oxide/metal oxide target compositions with rhenium in a lower, relatively reduced oxidation state are prepared. The thin-film rhenium targets are aged for at least about 24 hours and then irradiated with neutrons in the present of an oxidizing medium sufficient to form a product nuclide in the higher oxidized state of perrhenate, ReO,. Significantly, the rate and/or extent of oxidation of target nuclides which do not react with a neutron is controlled. For example, oxidation of such non-bombarded target nuclides is minimized by irradiating under vacuum, controlling the amount of oxidizing agent present, cooling during irradiation, etc. The product nuclide is recovered by dissolving the perrhenate in a non-oxidizing solvent such as water or saline.

Production of 186Re, 188Re and other radionuclides via inorganic Szilard-Chalmers process

Methods for the production of radionuclides suitable for use in radiopharmaceuticals for diagnostic and therapeutic applications, and specifically, to the production of .sup.186 Re, .sup.188 Re and other radionuclides such as .sup.195m Pt and .sup.198 Au using an inorganic Szilard-Chalmers reaction. Thin-film and powdered .sup.185 or 187 Re.degree. metal targets, and .sup.185 or 187 Re oxide/metal oxide target compositions with rhenium in a lower, relatively reduced oxidation state are prepared. The thin-film rhenium targets are aged for at least about 24 hours and then irradiated with neutrons in the present of an oxidizing medium sufficient to form a product nuclide in the higher oxidized state of perrhenate, ReO.sub.4.sup.-. Significantly, the rate and/or extent of oxidation of target nuclides which do not react with a neutron is controlled. For example, oxidation of such non-bombarded target nuclides is minimized by irradiating under vacuum, controlling the amount of oxidizing agent present, cooling during irradiation, etc. The product nuclide is recovered by dissolving the perrhenate in a non-oxidizing solvent such as water or saline.

Production of .sup.186 Re, .sup.188 Re and other radionuclides via

A radiolabeled protein composition adapted for radiation therapy which comprises a radioisotope and a protein material containing about 6 or more percent amino acids which have a sulfhydryl-containing side chain. A method for carrying out radiation synovectomy of arthritic joints. Rhenium radiolabeled protein microspheres are administered which contain cysteine and other amino acids. A method for radiolabeling a protein composition whereby the composition is treated with a reducing agent capable of reducing disulfides to sulfhydryls prior to radiolabeling.

Radiolabeled protein composition and method for radiation synovectomy

Process for preparing a radionuclide generator for producing Tc-99m or Re-188. A clear solution containing a metallic cation and an anion comprising W-188 or Mo-99 is provided. The metallic cation is present in the solution as a dissolved complex of the metallic cation and a complexing agent and/or the anion being present in the solution as a dissolved complex of the anion and a complexing agent. The dissolved complex(es) are decomposed to form a slurry containing a precipitate of the metallic cation and the anion. The precipitate is transferred to an elutable container of a radionuclide generator.

Process for the preparation of rhenium-188 and technetium-99m generators

Microspheres for radiation therapy of a mammal which have a non-radioactive isotope which emits beta or gamma radiation of therapeutic intensity upon being irradiated. The microspheres also contain elements which do not become radioactive upon irradiation. The chemical durability of the microspheres is such that they do not release a significant amount of radiation emitting radioisotope into the mammal's system upon administration. Microspheres containing phosphorus or yttrium; and carbon, nitrogen, fluorine, sodium, magnesium, aluminum, silicon, potassium, vanadium, manganese, gallium, niobium, iodine and/or lead.

Microspheres for radiation therapy

A method and a generator for separating daughter radioisotope from a stock solution containing the daughter radioisotope and its parent are provided. The generator is provided with a glass adsorbent which preferentially adsorbs daughter radioisotope relative to the parent radioisotope and circulation means for withdrawing the stock solution from a reservoir, contacting the solution with the glass adsorbent to adsorb the daughter radioisotope and returning the parent radioisotope-enriched solution to the reservoir. In the process stock solution containing daughter radioisotope having a predetermined pH is contacted with the glass adsorbent to selectively adsorb the daughter radioisotope thereon and the daughter radioisotope is eluted with an eluant at a second predetermined pH. The process also includes a step of washing the glass adsorbent with a wash solution at the first predetermined pH to remove traces of the parent radioisotope from the adsorbent prior to eluting the daughter radioiotope. In the process the first predetermined pH is in the range of from 4.0 to 10.0 and the second predetermined pH is less than 4. Daughter radioisotopes such as Y-90, Ga-68 and Ca-47 can be separated from their parents using these process and generator.

Method and apparatus for the generation of radioisotopes

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.

A method for preparing nonradioactive microspheres adapted for radiation synovectomy of arthritic joints in a mammal involves forming the microspheres by doping a biodegradable glass material which may be lithium or potassium silicate, lithium or potassium aluminosilicate, lithium or potassium aluminoborate, lithium or potassium germanate or lithium or potassium aluminogermanate with an isotope which may be samarium, holmium, erbium, dysprosium, rhemium or yttrium so that the isotope is chemcially dissolved in and distributed uniformly throughout the glass material. The doped glass material is then treated with an acid wash to produce a thin layer on the surface thereof and heat treated to improve the chemical durability of the glass material by rendering the solubility of the layer lower than that of the underlying glass material.

Composition and method for radiation synovectomy of arthritic joints

Radioactive microspheres for radiation synovectomy of arthritic joints in a mammal comprises a biodegradable glass material and a beta radiation emitting radioisotope chemically dissolved in and distributed substantially uniformly throughout the glass material. The biodegradable glass material may be lithium silicate, lithium aluminosilicate, lithium aluminoborate, lithium germanate, lithium aluminogermanate, potassium silicate, potassium aluminosilicate, potassium aluminoborate, potassium germanate or potassium aluminogermanate and the beta radiation emitting radioisotope may be samarium-153, holmium-166, erbium-169, dysprosium-165, rhenium-186, rhenium-188 or yttrium-90. Method for preparing such microspheres and for carrying out radiation synovectomy of arthritic joints utilizing such microspheres are also disclosed.

A radioactive microsphere for radiation therapy of a mammal comprising a biologically compatible glass material containing a beta or gamma emitting radioisotope distributed substantially uniformly throughout the glass. Advantageously, the radioisotope is produced by irradiation of the microsphere.

Radioactive glass microspheres

Radioactive microspheres for radiation synovectomy of arithmetic joints in a mammal comprise a biodegradable glass material and a beta radiation emitting radioisotope chemically dissolved in and distributed substantially uniformly throughout the glass material. The biodegradable glass material may be lithium silicate, lithium aluminosilicate, lithium aluminoborate, lithium germanate, lithium aluminogermanate, potassium silicate, potassium aluminosilicate, potassium, aluminoborate, potassium germanate or potassium aluminogermanate and the beta radiation emitting radioisotope may be samarium-153, holmium-166, erbium-169, dysprosium-165, rhenium-186, rhenium-188 or yttrium-90. Methods for preparing such microspheres and for carrying out radiation synovectomy of arthritic joints utilizing such microspheres are also disclosed.

A process for preparing a tungsten-188/rhenium-188 generator having a tungstate matrix containing W-188 produced by irradiating tungsten-186 in the tungstate compound. High activity, carrier-free rhenium-188 may be obtained by elution. Substrates for further purifying the rhenium-188 eluate are also described.

Growing community of inventors

Columbia, MO, United States of America

Gary J Ehrhardt