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US 11,439,714 B2Granted
Radiopharmaceutical and methods
AssigneeCentre for Probe Development and Commercialization
InventorsJoe McCann, Justyna Kelly, Paul Billone
Life of this patent
Estimating the term…
Abstract
A radiopharmaceutical 177Lu-DOTATATE compound, a composition, and a kit are provided. Further provided are methods of synthesis of a 177Lu-DOTATATE compound and methods of treatment that comprise a 177Lu-DOTATATE compound.
Claims17
A single dosage pharmaceutical composition of 3.6 GBq to 11.1 GBq 177Lu-DOTATATE, comprising:
- (a) a complex of lutetium-177 and tetraazacyclododecane tetra-acetic acid-octreotate (DOTATATE) having 98% or greater lutetium-177 incorporation as determined by radio-iTLC;
- (b) one or more ascorbate compounds at a concentration of at least 50 mg/mL, and one or more gentistate compounds at a concentration of at least 15 mg/mL;
- wherein the pharmaceutical composition has a radioactive concentration of 0.96 GBq/mL or less and maintains a radiochemical purity of 95% or greater as determined by radio-HPLC after 5 days at 25° C.
A method for preparing 177Lu-DOTATATE, comprising:
- forming an incorporation reaction mixture comprising lutetium-177 and tetraazacyclododecane tetra-acetic acid-octreotate (DOTATATE) in the presence of one or more ascorbate compounds and one or more gentistate compounds, wherein the ascorbate compound(s) are provided at a concentration of at least 50 mg/mL in the incorporation reaction mixture, the gentistate compound(s) are provided at a concentration of at least 15 mg/mL in the incorporation reaction mixture, and the lutetium-177 is present in the incorporation reaction mixture at a radioactive concentration of about 3.36 GBq/mL,
- heating the incorporation reaction mixture to 80° C. or less thereby forming a complex of lutetium-177 and tetraazacyclododecane tetra-acetic acid-octreotate (DOTATATE) having 98% or greater lutetium-177 incorporation as determined by radio-iTLC;
- after cooling the incorporation reaction mixture, diluting the incorporation reaction mixture to form a pharmaceutical preparation comprising the complex at a radioactive concentration of 0.96 GBq/mL or less, and having a final concentration of ascorbate compound(s) of at least 50 mg/mL, and of gentistate compound(s) of at least 15 mg/mL, wherein the pharmaceutical composition maintains a radiochemical purity of 95% or greater as determined by radio-HPLC after 5 days at 25° C.
A method for treating a patient suffering from cancer, comprising:
- (a) forming an incorporation reaction mixture comprising lutetium-177 and an aqueous formulation comprising tetraazacyclododecane tetra-acetic acid-octreotate (DOTATATE) in the presence of one or more ascorbate compounds and one or more gentistate compounds, wherein the one or more ascorbate compounds are provided at a concentration of at least 50 mg/mL in the incorporation reaction mixture, and the one or more gentisate compounds are provided at a concentration of at least 15 mg/mL in the incorporation reaction mixture,
- heating the incorporation reaction mixture to 80° C. or less thereby forming a complex of lutetium-177 and tetraazacyclododecane tetra-acetic acid-octreotate (DOTATATE) having 98% or greater lutetium-177 incorporation as determined by radio-iTLC, and
- after cooling the incorporation reaction mixture, diluting the incorporation reaction mixture to form a pharmaceutical preparation comprising the complex at a radioactive concentration of 0.96 GBq/mL, and having a final concentration of ascorbate compound(s) of at least 50 mg/mL, and of gentistate compound(s) of at least 15 mg/mL,
- wherein the pharmaceutical composition maintains a radiochemical purity of 95% or greater as determined by radio-HPLC after 5 days at 25° C.;
- and ;
- and
- b) administering the pharmaceutical preparation to the patient.
4 more elements
A single dosage pharmaceutical composition of 3.6 GBq to 11.1 GBq 177LU-DOTATATE, comprising:
- a complex of lutetium-177 and tetraazacyclododecane tetra-acetic acid-octreotate (DOTATATE) having 98% or greater lutetium-177 incorporation as determined by radio-iTLC, being formed from an incorporation reaction carried out at a temperature of 80° C. or less in a solution including at least 15 mg/mL of one or more gentistate compounds and at least 50 mg/mL of one or more ascorbate compounds;
- which complex, after formation in the incorporation reaction, is admixed to form the pharmaceutical composition having a concentration of at least 15 mg/mL of one or more gentistate compounds and at least 50 mg/mL of one or more ascorbate compounds, wherein the pharmaceutical composition maintains after 5 days at 25° C. following preparation of the composition:
- i) a radioactive concentration of 0.96 GBq/mL or less and ii) a radiochemical purity of 95% or greater as determined by radio-HPLC.
Dependencies are inferred from the claim text.