Neorx Corporation

University of Cincinnati

Other

Jean-Luc VanderHeyden

Alan R Fritzberg

Sudhakar Kasina

Ananthachari Srinivasan

Tripuraneni N Rao

Fu-Min Su

Edward A Deutsch

Joseph E Bugaj

Prasanna Venkatesan

Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy.

Metal-radionuclide-labeled proteins and glycoproteins for diagnosis and

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

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

Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy. Chelating compounds are disclosed.

Chelating compounds for metal-radionuclide labeled proteins

A cationic .sup.99m Tc.sup.III myocardial imaging agent is disclosed which has a relatively negative redox potential. This prevents in vivo reduction of the Tc(III) to Tc(II). The redox potential of the Tc(III) is controlled by complexing the Tc with both hard and soft atoms. Preferably four of the atoms complexed to the Tc(III) are hard atoms such as nitrogen or oxygen and the remaining two are soft atoms such as phosphorous or arsenic. These imaging agents are particularly useful in imaging the human heart.

.sup.99m Tc.sup.(III) myocardial imaging agents which are non-reducable

Pure perihenate is isolated from a aqueous crude solution of perrhenate by first associating the perrherate with a lipophilic counter ion such as tetrabutyl ammonium. This is added to the solution in a form such as tetrabutyl ammonium bromide. Tetrabutyl ammonium perrhenate is formed. The aqueous mixture is then added to a reverse phase separation column such as a C.sub.18 Sep Pak filter which has been previously loaded with the lipophilic counter ion. The aqueous portion of the crude mixture is eluted from the column with water. Subsequently the purified perrhenate associated with the lipophilic counter ion is removed with a less polar solvent such as ethanol. Pertechnetate can also be separated from an aqueous mixture in the same manner. These procedures are particularly suited for isolating relatively pure radioactive forms of perrhenate and pertechnetate such as Re.sup.186 O.sub.4.sup.-, Re.sup.188 O.sub.4.sup.-, and .sup.99m TcO.sub.4.sup.-.

Growing community of inventors

Seattle, WA, United States of America

Jean-Luc VanderHeyden