CLOSED EVAPORATION SYSTEM
20200043620 ยท 2020-02-06
Inventors
Cpc classification
C07C229/36
CHEMISTRY; METALLURGY
B01J19/0093
PERFORMING OPERATIONS; TRANSPORTING
C07B59/00
CHEMISTRY; METALLURGY
B01D1/30
PERFORMING OPERATIONS; TRANSPORTING
C07C229/48
CHEMISTRY; METALLURGY
C07B2200/05
CHEMISTRY; METALLURGY
C07B59/005
CHEMISTRY; METALLURGY
C07J1/007
CHEMISTRY; METALLURGY
C07C229/48
CHEMISTRY; METALLURGY
International classification
G21G1/00
PHYSICS
C07J1/00
CHEMISTRY; METALLURGY
C07B59/00
CHEMISTRY; METALLURGY
B01J19/00
PERFORMING OPERATIONS; TRANSPORTING
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.
Claims
1-21. (canceled)
22. A method for the synthesis of a radiolabelled compound wherein said method comprises: (i) radiolabelling a protected precursor compound in a fixed volume container 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; and, (iv) heating the radioactive fluid in the fixed volume container above its boiling point to reach the equilibrium gas/liquid phase causing said liquid to vaporise 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.
23. The method as defined in claim 22 wherein said fixed volume container is a reaction vessel.
24. The system as defined in claim 22 wherein said expandable volume is a syringe.
25. The method as defined in claim 22 wherein said radiolabelled compound is a radiopharmaceutical.
26. The method as defined in claim 25 wherein said radiopharmaceutical is a diagnostic radiopharmaceutical.
27. The method as defined in claim 26 wherein said diagnostic radiopharmaceutical is either a single photon emission tomography (SPECT) tracer or a positron emission tomography (PET) tracer.
28. The method as defined in claim 27 wherein said diagnostic radiopharmaceutical is a PET tracer.
29. The method as defined in claim 28 wherein said PET tracer comprises a .sup.11C-labelled compound or an .sup.18F-labelled compound.
30. The method as defined in claim 29 wherein said .sup.18F-labelled compound is selected from [.sup.18F]fluorodeoxyglucose ([.sup.18F]FDG), [.sup.18F]fluorothymidine ([.sup.18F]FLT), anti-1-amino-3-[.sup.18F]fluorocyclobutyl-1-carboxylic acid ([.sup.18F]FACBC), [.sup.18F]fluoromisonidazole ([.sup.18F]FMISO), [.sup.18F]fluoro-L-DOPA ([.sup.18F]DOPA), O-(-2-[.sup.18F]fluoroethyl)-L-tyrosine ([.sup.18F]FET), 16-[.sup.18F]fluoro-17-estradiol ([.sup.18F]FES) and [.sup.18F]-1-(5-fluoro-5-deoxy--aribinofuranosyl)-2-nitroimidazole ([.sup.18F]-FAZA).
31. The method as defined in claim 30 wherein said .sup.18F-labelled compound is selected from [.sup.18F]FDG [.sup.18F]FLT, [.sup.18F]FACBC and [.sup.18F]FMISO.
32. The method as defined in claim 31 wherein said .sup.18F-labelled compound is [.sup.18F]FLT.
Description
BRIEF DESCRIPTION OF THE FIGURES
[0049]
[0050]
[0051]
BRIEF DESCRIPTION OF THE EXAMPLES
[0052] Example 1(i) describes synthesis of non-radioactive FLT using FASTlab to assess acetonitrile residual content.
[0053] Example 1(ii) describes synthesis of [.sup.18F]FLT using FASTlab to assess the amount of volatile radioactive material generated.
LIST OF ABBREVIATIONS USED IN THE EXAMPLES
[0054] FLT fluorothymidine
sec second(s)
mBar millibar(s)
ppm parts per million
EXAMPLES
Example 1: Comparative View of Classical Vs. Inventive Evaporation Systems
[0055] Classical evaporation: 110 C., for 450 sec, 600 mBar (vacuum pump set point), N.sub.2 pressurelow flow valve [0056] Closed evaporation system: 110 C., for 450 sec, the 6 ml syringe is emptied 3 times
Example 1(i) and Example 1(ii) below both use FASTlab and a cassette designed for the production of FLT.
1(i) Cold Runs to Assess the Acetonitrile Residual Content
[0057]
TABLE-US-00001 Method Residual acetonitrile (ppm) Closed evaporation system 2109 Closed evaporation system 1726 Closed evaporation system 2353 Classical evaporation 67030 Classical evaporation 47015 Classical evaporation 54342 Closed evaporation system 2309 Closed evaporation system 2661 Classical evaporation 97326 Classical evaporation 87924 Classical evaporation 88340 Mean Classical evaporation 73663 Closed evaporation system 2232
[0058] Conclusions: the closed evaporation systems results in a lower amount of acetonitrile as compared with the known evaporation method.
1(ii) Hot Runs to Assess the Activity Balance
TABLE-US-00002 Method Activity balance (%) Closed evaporation system 96.5% Closed evaporation system 96.37% Closed evaporation system 94.15% Classical evaporation 89.4% Mean Classical evaporation 89.4% Closed evaporation system 95.7%
[0059] Conclusions: the closed evaporation system reduces the amount of volatiles generated during the drying step.