	US 11,904,027 B2
	Stable, concentrated radionuclide complex solutions
Francesco de Palo, Ivrea (IT); Lorenza Fugazza, Ivrea (IT); Donato Barbato, Ivrea (IT); Maurizio Mariani, Ivrea (IT); Daniela Chicco, Albiano d'Ivrea (IT); Giovanni Tesoriere, Noicattaro (IT); and Clementina Brambati, Turin (IT)
Assigned to Advanced Accelerator Applications, Saint-Genis-Pouilly (FR)
Filed by Advanced Accelerator Applications, Rueil-Malmaison (FR)
Filed on Mar. 23, 2020, as Appl. No. 16/827,606.
Application 16/827,606 is a continuation of application No. 16/175,261, filed on Oct. 30, 2018, granted, now 10,596,276.
Application 16/175,261 is a continuation in part of application No. 16/140,962, filed on Sep. 25, 2018, abandoned.
Application 16/140,962 is a continuation in part of application No. 16/045,484, filed on Jul. 25, 2018, abandoned.
Prior Publication US 2020/0353106 A1, Nov. 12, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 51/00 (2006.01); A61M 36/14 (2006.01); A61K 51/04 (2006.01); C22B 59/00 (2006.01); A61K 33/24 (2019.01)

CPC A61K 51/048 (2013.01) [A61K 33/24 (2013.01); C22B 59/00 (2013.01); A61K 51/0482 (2013.01)]

26 Claims

1. A process for manufacturing a pharmaceutical aqueous solution, comprising:

providing a solution comprising a complex of the radionuclide ¹⁷⁷Lu (Lutetium-177) and a somatostatin receptor binding peptide linked to the chelating agent DOTA; a first stabilizer against radiolytic degradation, and optionally a second stabilizer against radiolytic degradation different from the first stabilizer; and

diluting the solution comprising the complex with an aqueous dilution solution comprising at least one stabilizer against radiolytic degradation to obtain the pharmaceutical aqueous solution;

wherein if the solution comprising the complex comprises only the first stabilizer and not the second stabilizer, then the aqueous dilution solution comprises at least one stabilizer that is different from the first stabilizer, and in the obtained pharmaceutical aqueous solution, the radionuclide ¹⁷⁷Lu is present in a concentration that it provides a volumetric radioactivity of from 250 to 500 MBq/mL the first stabilizer is present in a concentration of from 0.5 to 2 mg/mL and the concentration ratio between the first and second stabilizers is between 1:3 to 1:7, and wherein ethanol is present in the pharmaceutical aqueous solution in a concentration of less than 1%.