PET Tracer Purification System

Patent metadata

Field	Value
Publication number	US-2017313632-A1
Application number	US-201515526245-A
Country	US
Kind code	A1
Filing date	Nov 12, 2015
Priority date	Nov 12, 2014
Publication date	Nov 2, 2017
Grant date	—

Abstract

The present invention provides a new chemical process, a new cassette configuration, and new software for the automated production of multiple batches of an [ 18 F]-labelled compound on a single cassette. The invention allows one synthesizer in one hot cell to produce sequentially a plurality of batches of [ 18 F]-labelled PET tracer in the same day. In particular, the present invention provides a novel arrangement useful for purifying two consecutive batches of a reaction mixture comprising an 18 F-labelled compound.

First claim

1 . A system for purifying two consecutive batches of a reaction mixture comprising an 18 F-labelled compound, said system comprises:
(i) a reversed-phase solid phase extraction (SPE) column having a first end and a second end, wherein each of said first end and said second end is selectively fluidly connected to a common pathway; and (ii) first and second normal-phase SPE columns, each having a first end selectively fluidly connected to said common pathway and a second end fluidly connected to a product collection vial.

2 . The system of claim 1 , wherein the chemistry of said reversed-phase SPE column is selected from octadecyl (C18 or tC18), octyl (C8), cyano (CN), diol, hydrophilic modified styrene polymer (HLB), polymeric poly(divinylbenzene-vinylpyrrolidone) and NH 2 .

3 . The system of claim 1 , wherein said reversed-phase SPE column is selected from a tC18 column and a HLB column.

4 . The system of claim 1 , wherein said reversed-phase SPE column is a tC18 column.

5 . The system of claim 1 , wherein each of said first and second normal-phase SPE columns is an alumina SPE column.

6 . The system of claim 1 , wherein the system is part of a single-use cassette for the synthesis of said 18 F-labelled compound.

7 . The system of claim 6 , wherein said single-use cassette is a FASTlab™ cassette.

8 . The system of claim 1 , wherein said 18 F-labelled compound 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.

9 . The system of claim 1 , wherein said 18 F-labelled compound is selected from [ 18 F]FDG, [ 18 F]FMISO, [ 18 F]FLT and [ 18 F]FACBC.

10 . A single-use cassette for preparing two consecutive batches of an [ 18 F]-labelled compound, said cassette comprises:
(a) a reversed-phase SPE column having a first end and a second end, wherein each of said first end and said second end is selectively fluidly connected to a common pathway, and means for cleaning said SPE column; and, (b) first and second normal-phase SPE columns, each having a first end selectively fluidly connected to said common pathway and a second end fluidly connected to a product collection vial; (c) two anion exchange SPE columns; (d) a reaction vessel and means for cleaning said reaction vessel; (e) a vial containing sufficient eluent for said two consecutive batches; (f) a vial containing sufficient precursor compound for said two consecutive batches; (g) reagent vials each containing a particular reagent in sufficient quantity for said two consecutive batches; and (h) a SPE column for deprotection and means for cleaning said SPE column.

11 . The cassette of claim 10 , wherein said reversed-phase SPE column is selected from octadecyl (C18 or tC18), octyl (C8), cyano (CN), diol, hydrophilic modified styrene polymer (HLB), polymeric poly(divinylbenzene-vinylpyrrolidone) and NH 2 .

12 . The cassette of claim 10 , wherein said reversed-phase SPE column is selected from a tC18 and a HLB SPE column.

13 . The cassette of claim 10 , wherein said reversed-phase SPE column is a tC18 column.

14 . The single use cassette of claim 10 , wherein each of said first and second normal-phase SPE columns is an alumina SPE column.

15 . The cassette of claim 10 , wherein each of said anion exchange SPE columns is a quaternary ammonium anion exchange (QMA) column.

16 . The cassette of claim 10 , wherein each of said means for cleaning comprises a source of sterile water and/or a source of an organic solvent selectively fluidly connected respectively to said reversed-phase SPE column, said reaction vessel, and said SPE column for deprotection.

17 . The cassette of claim 10 , wherein said eluent comprises a cationic counterion dissolved in an organic-aqueous solution.

18 . The cassette of claim 17 , wherein said cationic counterion is selected from rubidium, caesium, potassium complexed with a cryptand and a tetraalkylammonium salt.

19 . The cassette of claim 17 , wherein said cationic counterion is potassium complexed with a cryptand.

20 . The cassette of claim 19 , wherein said cryptand is 4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (Kryptofix™ 222).

21 . The cassette of claim 10 , wherein said reagent vials comprise a vial containing ethanol, a vial containing acetonitrile, a vial containing a deprotecting agent, and a vial containing buffer.

22 . The cassette of claim 21 , wherein said deprotecting agent is selected from HCl, NaOH, and H 3 PO 4 .

23 . The cassette of claim 21 , wherein said deprotecting agent is NaOH.

24 . The cassette of claim 21 , wherein said buffer is based on a weak acid.

25 . The cassette of claim 21 , wherein said buffer is selected from citrate, phosphate, acetate and ascorbate.

26 . The cassette of claim 21 , wherein said buffer is citrate buffer or phosphate buffer.

27 . The cassette of claim 10 , wherein said SPE column for deprotection is a reversed-phase SPE column.

28 . The cassette of claim 27 , wherein said reversed-phase column is a tC18 column.

29 . The cassette of claim 28 , wherein said tC18 column is an environmental tC18 column.

30 . The cassette of claim 10 , wherein said 18 F-labelled compound 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, [ 18 F]-fluoro-3-iodobenzyl guanidine([ 18 F]-FIBG), meta-[ 18 F]fluorobenzylguanidine([ 18 F]-mFBG) and [ 18 F]-5-fluorouracil.

31 . The cassette of claim 10 , wherein said 18 F-labelled compound is selected from [ 18 F]FDG, [ 18 F]FMISO, [ 18 F]FLT, and [ 18 F]FACBC.

32 . The cassette of claim 10 , wherein said 18 F-labelled compound is [ 18 F]FDG.

33 . A method for purifying a first batch and a second batch of a reaction mixture comprising an 18 F-labelled compound, said method comprises:
(I) passing said first batch of said reaction mixture through a reversed-phase SPE column; (II) eluting said reversed-phase SPE column to obtain a partially purified first batch of said reaction mixture; (III) passing said partially purified first batch of said reaction mixture through a first normal-phase SPE column; (IV) eluting said first normal-phase SPE column to obtain a purified first batch of said reaction mixture; (V) passing said purified first batch of said reaction mixture into a product collection vial; (VI) cleaning said reversed-phase SPE column; and, (VII) passing said second batch of said reaction mixture through said cleaned reversed-phase SPE column; (VIII) eluting said reversed-phase SPE column to obtain a partially purified second batch of said reaction mixture; (IX) passing said part

Assignees

• Ge Healthcare Ltd

Inventors

• Franci Xavier
• Lignon Steve
• Lange Audrey Marie
• Verbrugge Nicolas

Classifications

• C07B59/00 Primary

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

• B01D15/325

  Reversed phase · CPC title

• B01D15/363

  Anion-exchange · CPC title

• B01D15/322

  Normal bonded phase · CPC title

• C07H5/02

  to halogen · CPC title