Synthesis of a radioactive agent composition
AssigneeLaboratoires Cyclopharma
InventorGilles Viot
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Abstract
The present invention relates to a method for the synthesis of a radioactive agent composition comprising at least a purification step carried out in the presence of an antioxidant, to the composition obtained by this method comprising radioactive agent and excipient, and to the method for preventing radiolysis of radioactive agent composition comprising the synthesis of said radioactive agent according to the method of the invention.
Claims19
A method for the synthesis of a radioactive agent composition, the method comprising:
- i) providing an amount of 18F− with a radioactivity in the range of 79-450 GBq;
- ii) providing a precursor;
- iii) combining the precursor and the 18F−, performing nucleophilic substitution, and performing hydrolysis, thereby performing synthesis of 16α-[18F]fluoro-17β-estradiol:
- wherein the synthesis is performed in the presence of an antioxidant;
- iv) performing at least chromatographic purification of the 16α[18F]fluoro-17β-estradiol in the presence of an antioxidant;
- and
- v) formulating the 16α-[18F]fluoro-17β-estradiol with excipient in the presence of an antioxidant to obtain a formulation with 16α-[18F]fluoro-17β-estradiol suitable for imaging;
- wherein the synthesis, purification, and formulating are performed in a manner to inhibit radiolysis and provide the 16α-[18F]fluoro-17β-estradiol formulation with a radiochemical purity of at least 95% and stability for at least 10 hours, wherein the antioxidant is selected from the group consisting of ascorbic acid, polyphenols, glutathione, tocopherol, caffeic acid, alkali metal salts or alkaline earth metal salts of ascorbic acid.
A method for the synthesis of a radioactive agent composition, the method comprising:
- obtaining 18F− from irradiated 18O water by processing the irradiated 18O water with an ion exchange resin cartridge;
- synthesizing 16α-[18F]fluoro-17β-estradiol by combining the 18F− with a precursor in acetonitrile, performing hydrolysis, and adding sodium ascorbate;
- processing the 16α-[18F]fluoro-17β-estradiol with a first reversed-phase cartridge, then HPLC, then with a second reversed-phase cartridge, each performed in the presence of sodium ascorbate;
- and
- formulating an intravenous injectable solution of the 16α-[18F]fluoro-17β-estradiol comprising sodium ascorbate and ethanol.
A method for the synthesis of a radioactive agent composition, the method comprising:
- a) synthesis of 16α-[18F]fluoro-17β-estradiol by:
- forming an 18-fluoride-tetrabutylammonium (TBA) complex from 18F− and tetrabutylammonium (TBA) carbonate;
- performing a nucleophilic substitution reaction with a precursor and the 18-fluoride-tetrabutylammonium (TBA) complex to obtain a fluorinated product;
- and
- hydrolyzing the fluorinated product to obtain 16α-[18F]fluoro-17β-estradiol and dilution with an aqueous solution of sodium ascorbate;
- b) purification of the 16α-[18F]fluoro-17β-estradiol by:
- performing a pre-HPLC purification and washing with an aqueous solution of sodium ascorbate;
- performing high pressure liquid chromatography (HPLC) with an eluent comprising sodium ascorbate and ethanol;
- and
- collecting the 16α-[18F]fluoro-17β-estradiol and diluting in an aqueous solution of sodium ascorbate;
- c) formulation of a composition comprising the 16α-[18F]fluoro-17β-estradiol by:
- removing HPLC solvent by performing post-HPLC purification, washing with an aqueous solution of sodium ascorbate, and eluting with ethanol;
- and
- diluting with sodium chloride containing sodium ascorbate to obtain the 16α-[18F]fluoro-17β-estradiol in an isotonic solution.
Dependencies are inferred from the claim text.