Stable, concentrated radionuclide complex solutions
AssigneeAdvanced Accelerator Applications SA
InventorsDonato Barbato, Clementina Brambati, Daniela Chicco, Francesco de Palo, Lorenza Fugazza, Maurizio Mariani, Giovanni Tesoriere
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Abstract
The present invention relates to radionuclide complex solutions of high concentration and of high chemical stability, that allows their use as drug product for diagnostic and/or therapeutic purposes. The stability of the drug product is achieved by at least one stabilizer against radiolytic degradation. The use of two stabilizers introduced during the manufacturing process at different stages was found to be of particular advantage.
Claims31
1-21. (canceled)
A process for manufacturing a pharmaceutical aqueous solution, the process comprising diluting an aqueous complex solution with an aqueous dilution solution to form the pharmaceutical aqueous solution;
- wherein the aqueous complex solution comprises:
- (a) a complex comprising (ai) radionuclide 177Lu (Lutetium-177), and (aii) DOTA-TATE or DOTA-TOC, and
- (b) at least one first stabilizer(s) against radiolytic degradation independently selected from gentisic acid and/or a salt thereof and ascorbic acid and/or a salt thereof;
- wherein the aqueous dilution solution comprises at least one second stabilizer(s) against radiolytic degradation which comprises ascorbic acid or a salt thereof;
- the first and second stabilizers are present in the pharmaceutical aqueous solution in a total concentration of 0.7 to 15 mg/ml;
- the activity of the pharmaceutical aqueous solution is 7.4 (±10%) GBq;
- the radionuclide is present in the pharmaceutical aqueous solution in a concentration that provides a volumetric radioactivity of 250 MBq/mL to 500 MBq/mL;
- and
- the pharmaceutical aqueous solution comprises less than 5% ethanol.
A method of treating a tumor in a patient in need thereof, the method comprising diluting an aqueous complex solution with an aqueous dilution solution to form a pharmaceutical aqueous solution and administering to the patient the pharmaceutical aqueous solution,
- wherein the aqueous complex solution comprises:
- (a) a complex comprising (ai) radionuclide 177Lu (Lutetium-177), and (aii) DOTA-TATE or DOTA-TOC, and
- (b) at least one first stabilizer(s) against radiolytic degradation independently selected from gentisic acid and/or a salt thereof and ascorbic acid and/or a salt thereof;
- wherein the aqueous dilution solution comprises at least one second stabilizer(s) against radiolytic degradation which comprises ascorbic acid or a salt thereof;
- the first and second stabilizers are present in the pharmaceutical aqueous solution in a total concentration of 0.7 to 15 mg/ml;
- the activity of the pharmaceutical aqueous solution is 7.4 (±10%) GBq;
- the radionuclide is present in the pharmaceutical aqueous solution in a concentration that provides a volumetric radioactivity of 250 MBq/mL to 500 MBq/mL;
- and
- the pharmaceutical aqueous solution comprises less than 5% ethanol.
Dependencies are inferred from the claim text.