Automatic process platform for the production of astatine-211 [At-211]-radiopharmaceuticals
A system and method for automatic production of astatine-211 labeled molecules is described. The invention represents a significant advantage in the preparation of At-211 radiopharmaceuticals including better reproducibility, reduced production time and increased radiation safety. The invention also enables routine automatic synthesis of radiopharmaceuticals in a clinical setting, in conjunction or at short distance from a cyclotron unit capable of producing the radionuclide.
1. A process for automatic synthesis of At-211 labeled molecules comprising:
isolating an At-211 nuclide from a solid irradiated Bi-209 target material;
dry-distilling the At-211 nuclide in a furnace system to provide a dry-distilled At-211;
condensing the dry-distilled At-211 by cooling in a cooling unit to obtain as a dry residue At-211;
eluting the dry residue At-211 with a transfer liquid that solvates the dry residue At-211 to provide an At-211 solvate;
introducing the At-211 solvate into a reaction vial, wherein said reaction vial comprises a precursor molecule adapted to bind At-211;
activating the At-211 in the At-211 solvate for to provide an activated At-211;
reacting the activated At-211 with said precursor molecule to provide the At-211 labeled molecules,
wherein the process is automatic from isolation of the At-211 nuclide to providing the At-211 labeled molecules.
2. The process of claim 1 , wherein automatically isolating the At-211 nuclide from the solid irradiated Bi-209 target material comprises scraping the solid irradiated bismuth Bi-209 target material to obtain an At-211 powder target material comprising the At-211 nuclide.
3. The process of claim 2 , wherein the scraping of the solid irradiated Bi-209 target material is performed using a scraping unit.
4. The process of claim 1 , wherein the transfer liquid is an organic solvent.
5. The process of claim 4 , wherein the organic solvent is evaporated from the reaction vial leaving a dry residue of At-211.
6. The process of claim 1 , wherein the transfer liquid is an oxidizes the At-211 solvate.
7. The process of claim 1 , wherein the transfer liquid reduces the At-211 solvate.
8. The process of claim 1 , further comprising
purifying the At-211 labeled molecules to provide a purified product.
9. The process of claim 1 , wherein an inert gas is used to transport the dry-distilled At-211 from a receptacle of the furnace system to the cooling unit ( 106 ) and to transport the transfer liquid within the furnace system.
10. The process of claim 1 , wherein a reduced pressure is applied while dry-distilling the At-211 nuclide to confine At-211 in the furnace system and to speed up rate of distillation.
11. The process of claim 1 , wherein the cooling unit is a cryotrap.
12. The process of claim 1 , wherein the precursor molecule is selected from the group comprising inorganic molecules, organic molecules such as non-proteins, proteins, peptides, antibodies or fragments thereof, and mixtures thereof.
13. The process of claim 8 , wherein the purifying is performed using a liquid chromatography or a high pressure liquid chromatography.
14. The process according to claim 1 , wherein the At-211 solvate comprises At-211 in one or more redox forms selected from the group comprising At-211<O>(ground form), At-211<n″>(reduced form) and At-211<m+>(oxidized form).
15. The process of claim 8 , further comprising sterile filtering the purified product.
16. The process of claim 2 , further comprising purifying the At-211 labeled molecules to provide a purified product.
17. The process of claim 16 , further comprising sterile filtering the purified product.
18. The process according to claim 4 , wherein an inert gas is used to transport the dry-distilled At-211 from a receptacle of the furnace system to the cooling unit and to transport the transfer liquid and the organic solvent within the furnace system.
19. The process according to claim 5 , wherein an inert gas is used to transport the dry distilled At-211 from a receptacle of the furnace system to the cooling unit and to transport the transfer liquid and the organic solvent within the furnace system.
20. The process according to claim 6 , wherein an inert gas is used to transport the dry distilled At-211 from a receptacle of the furnace system to the cooling unit and to transport the transfer liquid within the furnace system.
21. The process according to claim 7 , wherein an inert gas is used to transport the dry distilled At-211 from a receptacle of the furnace system to the cooling unit and to transport the transfer liquid within the furnace system.
22. The process according to claim 8 , wherein an inert gas is used to transport the dry distilled At-211 from a receptacle of the furnace system to the cooling unit and to transport transfer liquid within the furnace system.
23. The process according to claim 8 , wherein the purifying step is performed using a liquid chromatography or a high pressure liquid chromatography.
24. The process according to claim 9 , further comprising purifying the At-211 labeled molecules using a liquid chromatography or a high pressure liquid chromatography.