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US 9,061,996 B2Granted
Solid phase extraction method
AssigneeGe Healthcare Limited
InventorsDimitrios Mantzilas, Gry Helene Olaussen, Torild Wickstrom, Eric Horn, Imtiaz Khan
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Abstract
The present invention provides a method to prepare an 18F-labelled tricyclic indole compound comprising a solid-phase extraction (SPE) purification step. This method is particularly suitable for carrying out the radiofluorination method on an automated synthesizer. In addition to the radiofluorination method, the present invention provides a cassette designed to carry out the method on an automated synthesizer.
Claims23
A method to obtain a radiofluorinated compound of Formula I:
- wherein:
- R1 is hydrogen, halo or C1-3 alkoxy;
- R2 and R3 are independently methyl, ethyl or benzyl, or together with the nitrogen to which they are attached form a pyrrolidinyl, piperidinyl, azepanyl, or morpholinyl ring;
- Y1 is CH2, CH2—CH2, CH(CH3)—CH2, or CH2—CH2—CH2;
- and;
- n is 1, 2 or 3;
- wherein said method comprises:
- (i) providing a precursor compound of Formula Ia:
- wherein R1a-3a, Y1a and m are as defined for and are each the same as R1-3, Y1 and n of Formula I, respectively, and LG is a sulfonate leaving group;
- (ii) reacting said precursor compound of Formula Ia with a suitable source of [18F]-fluoride;
- (iii) purifying the reaction mixture obtained in step (ii), wherein said purifying step comprises:
- (a) providing one or more solid-phase extraction (SPE) cartridges wherein the sorbent comprises particles having a diameter between 10-120 μm and bonded hydrocarbons;
- (b) conditioning said one or more SPE cartridges;
- (c) loading the reaction mixture onto said one or more conditioned SPE cartridges;
- (d) washing said one or more SPE cartridges onto which said mixture is loaded using a first solvent system comprising a ratio of water:water-miscible organic solvent in the range 100:0-0:100;
- and,
- (e) eluting said one or more SPE cartridges following said washing step using a second solvent system comprising a ratio of water:water-miscible organic solvent in the range 70:30-0:100;
- with the proviso that in said purifying step HPLC is specifically excluded.
15 more elements
Dependencies are inferred from the claim text.