Stabilized compositions of radionuclides and uses thereof
Provided herein are radiopharmaceutical compositions and uses thereof. The radiopharmaceutical compositions can comprise one or more stabilizing agents, an aqueous vehicle, and a conjugate that comprises a targeting ligand and a radionuclide bound to a metal chelator. The targeting ligand can be a small molecule compound or a peptide such as a monocyclic peptide. The targeting ligand can be configured to bind with a tumor target. The stabilizing agent can comprise a radiolysis stabilizer, a free metal chelator, and/or a pH stabilizer. Further provided herein are methods of preparing the radiopharmaceutical compositions and methods of treating cancer by administering the described radiopharmaceutical compositions.
1. A liquid radiopharmaceutical composition comprising:
(a) 225 Ac-DOTA-TATE or a pharmaceutically acceptable salt thereof, wherein the 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof is present in the radiopharmaceutical composition at a concentration equivalent to 10 mCi/L to 30 mCi/L;
(b) sodium ascorbate, wherein the sodium ascorbate is present in the radiopharmaceutical composition at a concentration of 40 mM to 250 mM;
(c) diethylenetriamine pentaacetate (DTPA) wherein the DTPA is present in the radiopharmaceutical composition at a concentration of 0.01 mg/mL to 5 mg/mL; and
(d) an aqueous vehicle, wherein the aqueous vehicle is a saline solution;
wherein the radiopharmaceutical composition is a solution, and
wherein the radiopharmaceutical composition retains at least 90% of the 225 Ac content as 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof after 120 hours at about 20° C. to about 25° C.
2. The liquid radiopharmaceutical composition of claim 1 , wherein the 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof is present in the radiopharmaceutical composition at a concentration equivalent to 10 mCi/L to 25 mCi/L.
3. The liquid radiopharmaceutical composition of claim 1 , wherein the 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof is present in the radiopharmaceutical composition at a concentration equivalent to about 12 mCi/L to about 23 mCi/L.
4. The liquid radiopharmaceutical composition of claim 1 , wherein the 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof is present in the radiopharmaceutical composition at a concentration equivalent to about 40 μg to about 120 μg of the DOTA-TATE.
5. The liquid radiopharmaceutical composition of claim 1 , wherein the sodium ascorbate is present in the radiopharmaceutical composition at a concentration of 80 mM to 125 mM.
6. The liquid radiopharmaceutical composition of claim 1 , wherein the DTPA is present in the radiopharmaceutical composition at a concentration of 0.02 mg/mL to 2.5 mg/mL.
7. The liquid radiopharmaceutical composition of claim 1 , wherein the DTPA is present in the radiopharmaceutical composition at a concentration of 0.02 mg/mL to 0.07 mg/mL.
8. The liquid radiopharmaceutical composition of claim 1 , wherein the composition retains at least 90% of the 225 Ac content as 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof after 168 hours at about 20° C. to about 25° C.
9. The liquid radiopharmaceutical composition of claim 1 , wherein the composition retains at least 90% of the 225 Ac content as 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof after 192 hours at about 20° C. to about 25° C.
10. The liquid radiopharmaceutical composition of claim 1 , wherein the radiopharmaceutical composition is formulated as a unit dose form that contains about 12 mL of the solution.
11. The liquid radiopharmaceutical composition of claim 1 , comprising:
(a) 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof present in the radiopharmaceutical composition at a concentration equivalent to 10 mCi/L to 25 mCi/L;
(b) sodium ascorbate present in the radiopharmaceutical composition at a concentration of 80 mM to 125 mM;
(c) DTPA present in the radiopharmaceutical composition at a concentration of 0.01 mg/mL to 5 mg/mL; and
(d) sodium chloride saline solution.
12. The liquid radiopharmaceutical composition of claim 1 , wherein a pH of the liquid radiopharmaceutical composition is about 5.0 to about 7.0.
13. The liquid radiopharmaceutical composition of claim 1 , wherein the radiopharmaceutical composition is formulated for IV infusion.
14. The liquid radiopharmaceutical composition of claim 1 , wherein the 225 Ac-DOTA-TATE or the pharmaceutically acceptable salt thereof has a structure illustrated as
15. The liquid radiopharmaceutical composition of claim 1 , wherein the liquid radiopharmaceutical composition further comprises sodium acetate.
16. A method of treating a somatostatin receptor-positive (SSTR+) neuroendocrine tumor in a subject in need thereof, comprising administering to the subject an effective amount of a liquid radiopharmaceutical composition of claim 1 .
17. The method of claim 16 , wherein the neuroendocrine tumor is gastroenteropancreatic neuroendocrine tumor (GEP-NET).
18. The method of claim 16 , wherein, prior to the administrating of the liquid radiopharmaceutical composition, the subject received 177 Lu-DOTA-TATE or 177 Lu-DOTA-TOC treatment.
19. The method of claim 16 , wherein the radiopharmaceutical composition is administered to the subject in an amount equivalent to about 60 kBq/kg body weight to about 120 kBq/kg body weight per dose.