Closed evaporation system

Patent metadata

Field	Value
Publication number	US-11094424-B2
Application number	US-201916555484-A
Country	US
Kind code	B2
Filing date	Aug 29, 2019
Priority date	Oct 18, 2013
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

The present invention provides a system for evaporating a radioactive fluid, a method for the synthesis of a radiolabelled compound including this system, and a cassette for the synthesis of a radiolabelled compound comprising this system. The present invention provides advantages over known methods for evaporation of a radioactive fluid as it reduces drastically the amount of radioactive gaseous chemicals that are released in the hot cell. It is gentler and more secure compared to the known process and provides access to radiosyntheic processes that may not been acceptable for safety reasons related to release of volatile radioactive gases during evaporation. In addition, the process yields are higher because the radioactive volatiles are labelled intermediate species.

First claim

The invention claimed is:

1. A method for the automated synthesis of a radiolabelled compound within a cassette of an automated radiosynthesis apparatus wherein said method comprises:
(i) radiolabelling a protected precursor compound in a fixed volume container of the cassette to obtain a protected radiolabelled compound;
(ii) deprotecting the protected radiolabelled compound obtained from radiolabelling step (i) to obtain said radiolabelled compound wherein said deprotection is effected using a hydrolysis medium;
(iii) connecting the fixed volume container via a 3-way valve to an expandable volume of the cassette, wherein said expandable volume is within a syringe and said 3-way valve has a first position and a second position; and,
(iv) heating the radioactive fluid in the fixed volume container above its boiling point to reach the equilibrium gas/liquid phase while the 3-way valve is in the first position causing said liquid to vaporize and move into the expandable volume where it condenses due to the drop in temperature to form a volume of radioactive fluid in the expandable volume to form a condensed radioactive fluid, then positioning the 3-way valve to the second position to empty said condensed radioactive fluid to waste.

2. The method as defined in claim 1 wherein said fixed volume container is a reaction vessel.

3. The method as defined in claim 1 wherein said radiolabelled compound is a radiopharmaceutical.

4. The method as defined in claim 3 wherein said radiopharmaceutical is a diagnostic radiopharmaceutical.

5. The method as defined in claim 4 wherein said diagnostic radiopharmaceutical is either a single photon emission tomography (SPECT) tracer or a positron emission tomography (PET) tracer.

6. The method as defined in claim 5 wherein said diagnostic radiopharmaceutical is a PET tracer.

7. The method as defined in claim 6 wherein said PET tracer comprises a 11 C-labelled compound or an 18 F-labelled compound.

8. The method as defined in claim 7 wherein said 18 F-labelled compound is selected from [ 18 F]fluorodeoxyglucose ([ 18 F]FDG), [ 18 F]fluorothymidine ([ 18 F]FLT), anti-1-amino-3-[ 18 F]fluorocyclobutyl-1-carboxylic acid ([ 18 F]FACBC), [ 18 F]fluoromisonidazole ([ 18 F]FMISO), [ 18 F]fluoro-L-DOPA ([ 18 F]DOPA), O-(-2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET), 16a-[ 18 F]fluoro-1 78-estradiol ([ 18 F]FES) and [ 18 F]-1-(5-fluoro-5-deoxy-a-aribinofuranosyl)-2-nitroimidazole ([ 18 F]-FAZA).

9. The method as defined in claim 8 wherein said 18 F-labelled compound is selected from [ 18 F]FDG, [ 18 F]FLT, [ 18 F]FACBC and [ 18 F]FMISO.

10. The method as defined in claim 9 wherein said 18 F-labelled compound is [ 18 F]FLT.

11. The method as defined in claim 1 wherein the automated radiosynthesis apparatus controls the cassette from outside the cassette.

12. The method as defined in claim 1 wherein the cassette comprises a linear array of valves each linked to a port where reagents or vials can be attached.

13. The method as defined in claim 12 wherein the port is attached to the reagents or the vials by either a needle puncture of an inverted septum, a sealed vial, or a gas-tight marrying joint.

14. The method as defined in claim 11 wherein the syringe comprises a plunger and the automated radiosynthesis apparatus controls the plunger of the syringe to expand or collapse the expandable volume of the syringe.

15. The method as defined in claim 1 wherein the cassette comprises 15 to 40 valves in a linear array.

16. A method for the automated synthesis of a radiolabelled compound within a cassette of an automated radiosynthesis apparatus wherein said method comprises:
(i) radiolabelling a protected precursor compound in a reaction vessel of the cassette to obtain a protected radiolabelled compound;
(ii) deprotecting the protected radiolabelled compound obtained from radiolabelling step (i) to obtain said radiolabelled compound wherein said deprotection is effected using a hydrolysis medium, wherein the hydrolysis medium is an acidic or a basic solution;
(iii) connecting the fixed volume container via a 3-way valve to an expandable volume of the cassette and said 3-way valve has a first position and a second position, wherein said expandable volume is within a syringe and the syringe comprises a plunger whereby the automated radiosynthesis apparatus controls the plunger of the syringe to expand or collapse the expandable volume of the syringe; and,
(iv) heating the radioactive fluid in the reaction vessel above its boiling point to reach the equilibrium gas/liquid phase while the 3-way valve is in the first position causing said liquid to vaporize and move into the expandable volume of the syringe where it condenses due to the drop in temperature to form a volume of radioactive fluid in the expandable volume of the syringe to form a condensed radioactive fluid, then positioning the 3-way valve to the second position to empty said condensed radioactive fluid to waste.

17. The method as defined in claim 16 wherein said radiolabelled compound is a radiopharmaceutical.

18. The method as defined in claim 17 wherein said radiopharmaceutical is a diagnostic radiopharmaceutical.

19. The method as defined in claim 18 wherein said diagnostic radiopharmaceutical is either a single photon emission tomography (SPECT) tracer or a positron emission tomography (PET) tracer.

20. The method as defined in claim 19 wherein said PET tracer comprises a 11 C-labelled compound or an 18 F-labelled compound.

Assignees

• Ge Healthcare Ltd

Inventors

• Franci Xavier
• Lignon Steve
• Lange Audrey

Classifications

• G21F9/08 Primary

  by evaporation; by distillation · CPC title

• C07H19/06

  Pyrimidine radicals · CPC title

• B01J2219/00873

  Heat exchange · CPC title

• B01J2219/00885

  Thin film heaters · CPC title

• C07B59/00

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title