Purification method and compositions
AssigneeGe Healthcare Limited
InventorsTorgrim Engell, Andreas Meijer, Imtias Ahmed Khan, Robert James Nairne, Graeme McRobbie
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Abstract
The present invention relates to the field of radiopharmaceuticals for in vivo imaging, in particular to a method of purifying a radiotracer which comprises 18F-labelled aminoxy-functionalised biological targeting moiety. The invention provides radioprotectant-containing radiopharmaceutical compositions of the tracers, as well as associated automated methods and cassettes.
Claims9
1-19. (canceled)
A method of purification of a radiotracer which comprises the following steps:
- (a) provision of a crude radiotracer composition which comprises an 18F-labelled aminoxy functionalized biological targeting moiety (BTM), wherein the BTM is a c-Met binding cyclic peptide which comprises the amino acid sequence:
- -Cysa-X1-Cysc-X2-Gly-Pro-Pro-X3-Phe-Glu-Cysd-Trp-Cysb-Tyr-X4—X5—X6—
- wherein
- X1 is Asn, His or Tyr;
- X2 is Gly, Ser, Thr or Asn;
- X3 is Tor or Arg;
- X4 is Ala, Asp, Glu, Gly or Ser;
- X5 is Ser or Thr;
- X6 is Asp or Glu;
- and Cysa-d are each cysteine residues such that residues a and b as well as c and d are cyclized to form two separate disulfide bonds;
- (b) adding a formulation buffer that comprises a radioprotectant at a first concentration to said crude radiotracer composition to give a radiotracer solution which comprises said radiotracer in one or more aqueous water-miscible organic solvent(s) of 5 to 25% v/v organic solvent content;
- (c) passing the radiotracer solution from step (b) through a reverse phase SPE cartridge, wherein the radiotracer is retained on said SPE cartridge;
- (d) washing the SPE cartridge from step (c) one or more times with a wash solution which comprises an aqueous water-miscible organic solvent(s) solution of a radioprotectant of 15 to 25% v/v organic solvent content;
- (e) washing the SPE cartridge from step (d) one or more times with water or aqueous buffer solution;
- (f) eluting the washed SPE cartridge of step (d) or (e) with an elution solvent which comprises a radioprotectant in an aqueous ethanol solution having an ethanol content of 35 to 80% v/v, wherein the eluent comprises purified radiotracer in said elution solvent;
- wherein each radioprotectant independently comprises one or more of:
- ascorbic acid, para-aminobenzoic acid;
- and gentisic acid, and salts thereof with a biocompatible cation.
The method of claim 1, wherein the water-miscible organic solvent of the radiotracer solution comprises acetonitrile.
The method of claim 1, wherein the radiotracer solution of step (b) comprises 0.5 to 5% v/v ethanol.
The method of claim 1, wherein the SPE cartridge is a C18 SPE cartridge.
The method of claim 1, wherein the elution solvent of step (f) comprises 35 to 70% v/v aqueous ethanol.
The method of claim 1, wherein the elution solvent of step (f) comprises 40-60% v/v aqueous ethanol.
The method of claim 1, where the radioprotectant used in the radiotracer solution, wash solution and elution solvent is the same.
The method of claim 1, where the radioprotectant comprises 4-aminobenzoic acid, or a salt thereof with a biocompatible cation.
Dependencies are inferred from the claim text.