Dual run cassette for the synthesis of 18f-labelled compounds

Patent metadata

Field	Value
Publication number	US-2016257622-A1
Application number	US-201415033321-A
Country	US
Kind code	A1
Filing date	Nov 12, 2014
Priority date	Nov 13, 2013
Publication date	Sep 8, 2016
Grant date	—

Abstract

The invention provides a new chemical process, a new cassette configuration, and new software. The invention allows one synthesizer in one hot cell to produce sequentially two batches of [ 18 F]-labelled PET tracer in the same day.

First claim

1 . A cassette for the synthesis of a plurality of batches of an [ 18 F]-labelled positron-emission tomography (PET) tracer wherein said cassette comprises:
(i) an anion exchange column for each of said plurality of batches; (ii) a reaction vessel; (iii) a vial containing an aliquot of eluent for each of said plurality of batches; (iv) a vial containing an aliquot of a precursor compound for each of said plurality of batches; (v) reagent vials wherein each reagent vial contains an aliquot of reagent for each of said plurality of batches; (vi) optionally, a solid-phase extraction (SPE) column for deprotection and/or one or more SPE columns for purification; and, (vii) means for cleaning said reaction vessel and said SPE columns.

2 . The cassette as defined in claim 1 wherein said PET tracer is selected from [ 18 F]fluorodeoxyglucose ([ 18 F]FDG), [ 18 F]Fluoromisonidazole ([ 18 F]FMISO), [ 18 F]fluorothymidine ([ 18 F]FLT), [ 18 F]Fluoroazomycin arabinofuranoside ([ 18 F]FAZA), [ 18 F]Fluoroethyl-choline ([ 18 F]FECH), [ 18 F]fluorocyclobutane-1-carboxylic acid ([ 18 F]FACBC), [ 18 F]flumanezil ([ 18 F]FMZ), [ 18 F]tyrosine, [ 18 F]altanaserine, 4-[ 18 F]fluoro-3-iodobenzyl guanidine ([ 18 F]FIBG), meta-[ 18 F]fluorobenzylguanidine ([ 18 F]mFBG) and [ 18 F]5-fluorouracil.

3 . (canceled)

4 . (canceled)

5 . The cassette as defined in claim 1 wherein said anion exchange column is a quaternary ammonium anion exchange (QMA) column.

6 . The cassette as defined in claim 1 wherein said eluent comprises a cationic counterion dissolved in an organic-aqueous solution.

7 . (canceled)

8 . (canceled)

9 . (canceled)

10 . (canceled)

11 . (canceled)

12 . (canceled)

13 . (canceled)

14 . (canceled)

15 . (canceled)

16 . (canceled)

17 . (canceled)

18 . The cassette as defined in claim 1 wherein said means for cleaning said reaction vessel and said SPE columns comprises a source of water fluidly connected to said reaction vessel and to said SPE columns.

19 . The cassette as defined in claim 18 wherein said means for cleaning said reaction vessel and said SPE columns comprises a source of acetonitrile fluidly connected to said SPE column for deprotection.

20 . The cassette as defined in claim 19 wherein said means for cleaning said reaction vessel and said SPE columns comprises a source of ethanol fluidly connected to said SPE columns for purification.

21 . A method for the synthesis of a plurality of batches of an [ 18 F]-labelled PET tracer wherein said method comprises:
(a) trapping a first aliquot of [ 18 F]fluoride onto a first anion exchange column; (b) providing a first aliquot of a precursor compound in a reaction vessel; (c) passing a first aliquot of eluent through said first anion exchange column to elute said first aliquot of [ 18 F]fluoride into said reaction vessel; (d) heating the reaction vessel for a predetermined time to obtain crude [ 18 F]-labelled labelled PET tracer; (e) optionally deprotecting said crude [ 18 F]-labelled PET tracer on a SPE column; (f) optionally purifying said crude [ 18 F]-labelled PET tracer on one or more SPE columns; (g) cleaning said reaction vessel and said SPE columns; (h) repeating steps (a)-(g) one or more times, each time using a subsequent aliquot of [ 18 F]fluoride, a subsequent anion exchange column and a subsequent aliquot of a precursor compound; wherein said method is carried out on a single cassette.

22 . The method as defined in claim 21 wherein said PET tracer is selected from [ 18 F]fluorodeoxyglucose ([ 18 F]FDG), [ 18 F]Fluoromisonidazole ([ 18 F]FMISO), [ 18 F]fluorothymidine ([ 18 F]FLT), [ 18 F]Fluoroazomycin arabinofuranoside ([ 18 F]FAZA), [ 18 F]Fluoroethyl-choline ([ 18 F]FECH), [ 18 F]fluorocyclobutane-1-carboxylic acid ([ 18 F]FACBC), [ 18 F]flumanezil ([ 18 F]FMZ), [ 18 F]tyrosine, [ 18 F]altanaserine, 4-[ 18 F]fluoro-3-iodobenzyl guanidine ([ 18 F]FIBG), meta-[ 18 F]fluorobenzylguanidine ([ 18 F]mFBG) and [ 18 F]5-fluorouracil.

23 . (canceled)

24 . (canceled)

25 . The method as defined in claim 22 wherein each of said first anion exchange column and said subsequent anion exchange column is a quaternary ammonium anion exchange (QMA) column.

26 . The method as defined in claim 25 wherein said eluent comprises a cationic counterion dissolved in an organic-aqueous solution.

27 . (canceled)

28 . (canceled)

29 . (canceled)

30 . (canceled)

31 . (canceled)

32 . (canceled)

33 . (canceled)

34 . (canceled)

35 . (canceled)

36 . (canceled)

37 . (canceled)

38 . The method as defined in claim 26 wherein said cleaning step comprises rinsing said reaction vessel and said SPE columns with water.

39 . The method as defined in claim 38 wherein said cleaning step comprises rinsing said SPE column with acetonitrile prior to rinsing with water.

40 . The method as defined in claim 39 wherein said cleaning step comprises rinsing said SPE columns with ethanol prior to rinsing with water.

41 . A non-transitory storage medium comprising computer readable program code, wherein execution of the computer readable program code causes a processor to carry out the steps as defined in claim 40 .

Assignees

• Ge Healthcare Ltd

Inventors

• Franci Xavier

Classifications

• C07B59/00 Primary

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

• B01J2219/00731

  Saccharides · CPC title

• C07B59/005 Primary

  Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids · CPC title

• A61K51/04

  Organic compounds · CPC title

• A61K51/0491

  Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers · CPC title