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.
Claims30
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) the radionuclide 177Lu (Lutetium-177) and (aii) DOTA-TATE, and
- (b) at least one stabilizer(s) against radiolytic degradation selected from gentisic acid or a salt thereof and ascorbic acid or a salt thereof that is/are present in an amount to result in a concentration of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution;
- the aqueous dilution solution comprises at least one stabilizer(s) against radiolytic degradation selected from gentisic acid or a salt thereof and ascorbic acid or a salt thereof that is/are present in an amount to result in a concentration of 0.5 to 10 mg/ml in the pharmaceutical aqueous solution;
- and
- the radionuclide is present in the pharmaceutical aqueous solution in a concentration that provides a volumetric radioactivity of 250 to 500 MBq/mL;
- the radiochemical purity of the pharmaceutical aqueous solution as determined by HPLC can be maintained at ≥95% for at least 72 hours when stored at 25° C.;
- the activity of the pharmaceutical aqueous solution is 7.4 (±10%) GBq;
- and
- the pharmaceutical aqueous solution comprises less than about 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) the radionuclide 177Lu (Lutetium-177) and (aii) DOTA-TATE, and
- (b) at least one stabilizer(s) against radiolytic degradation selected from gentisic acid or a salt thereof and ascorbic acid or a salt thereof, that is/are present in an amount to result in a concentration of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution;
- the aqueous dilution solution comprises at least one stabilizer(s) against radiolytic degradation selected from gentisic acid or a salt thereof and ascorbic acid or a salt thereof, that is/are present in an amount to result in a concentration of 0.5 to 10 mg/ml in the pharmaceutical aqueous solution;
- and
- the radionuclide is present in the pharmaceutical aqueous solution in a concentration that provides a volumetric radioactivity of 250 to 500 MBq/mL;
- the radiochemical purity of the pharmaceutical aqueous solution as determined by HPLC can be maintained at ≥95% for at least 72 hours when stored at 25° C.;
- the activity of the pharmaceutical aqueous solution is 7.4 (±10%) GBq;
- and
- the pharmaceutical aqueous solution comprises less than about 5% ethanol.
Dependencies are inferred from the claim text.