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

Patent metadata

Field	Value
Publication number	US-10584078-B2
Application number	US-201415033321-A
Country	US
Kind code	B2
Filing date	Nov 12, 2014
Priority date	Nov 13, 2013
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

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

The invention claimed is:

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) a first anion exchange column for a first batch and a second anion exchange column for a second batch;
(ii) a reaction vessel;
(iii) a vial containing an aliquot of eluent for each of the batches;
(iv) a vial containing an aliquot of a precursor compound for each of the batches;
(v) reagent vials wherein each reagent vial contains an aliquot of reagent for each of the batches;
(vi) a reverse phase solid-phase extraction (SPE) column for deprotection and/or one or more normal phase SPE columns for purification; and,
(vii) means for cleaning said reaction vessel and said SPE columns, wherein the first anion exchange column, second anion exchange column, reaction vessel, vial containing an aliquot of eluent, vial containing an aliquot of precursor, reagent vials, reverse phase SPE column, one or more normal phase SPE columns, and means for cleaning are connected along a linear common pathway within the cassette.

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. The cassette as defined in claim 1 wherein said first anion exchange column and second anion exchange column are a quaternary ammonium anion exchange (QMA) columns.

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

5. 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.

6. The cassette as defined in claim 5 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.

7. The cassette as defined in claim 6 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.

8. A method for the synthesis of a plurality of batches of an [ 18 F]-labelled PET tracer in a cassette 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 PET tracer;
(e) deprotecting said crude [ 18 F]-labelled PET tracer on a reverse phase SPE column;
(f) purifying said crude [ 18 F]-labelled PET tracer on one or more normal phase SPE columns;
(g) cleaning said reaction vessel and said SPE columns;
(h) repeating steps (a)-(g) at least once, using a second aliquot of [ 18 F]fluoride, a second anion exchange column and a second aliquot of a precursor compound;

wherein the first anion exchange column, reaction vessel, vial containing an aliquot of eluent, vial containing an aliquot of precursor, reagent vial, reverse phase SPE column, the one or more normal phase SPE columns are connected along a linear common pathway within the cassette.

9. The method as defined in claim 8 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]altanasaltanase, 4-[ 18 F]fluoro-3-iodobenzyl guanidine ([ 18 F]FIBG), meta-[ 18 F]fluorobenzylguanidine ([ 18 F]mFBG) and [ 18 F]5-fluorouracil.

10. The method as defined in claim 9 wherein each of said first anion exchange column and said second anion exchange column is a quaternary ammonium anion exchange (QMA) column.

11. The method as defined in any one of claim 10 wherein said eluent comprises a cationic counterion dissolved in an organic-aqueous solution.

12. The method as defined in claim 11 wherein said cleaning step comprises rinsing said reaction vessel and said SPE columns with water.

13. The method as defined in claim 12 wherein said cleaning step comprises rinsing said SPE columns with acetonitrile prior to rinsing with water.

14. The method as defined in claim 13 wherein said cleaning step comprises rinsing said SPE columns with ethanol prior to rinsing with water.

Assignees

• Ge Healthcare Ltd

Inventors

• Franci Xavier

Classifications

• B01J19/0046

  Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays (synthesis methods per se C40B50/00) · CPC title

• B01J2219/00716

  Heat activated synthesis · CPC title

• B01J2219/00495

  Means for heating or cooling the reaction vessels · CPC title

• C07B59/00 Primary

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

• B01J2219/00731

  Saccharides · CPC title