Purification method
A diagnostic imaging agent useful for positron emission tomography (PET) imaging as well as to improved hardware for producing such imaging agents is described. Flutemetamol (18F) Injection for the imaging of b amyloid plaques in the brain and methods and devices for preparing same are described including the automated synthesis and purification of [18F]flutemetamol by means of solid phase extraction (SPE).
1. A purification process comprising the following steps:
(a) passing a diluted crude product reaction mixture comprising [18F]flutemetamol through a first reverse phase solid phase extraction (SPE) cartridge;
(b) washing said first reverse phase SPE cartridge with a water/acetonitrile, tetrahydrofuran(THF)/water, methanol(MeOH)/water or isopropanol/water mixture;
(c) rinsing said first reverse phase SPE cartridge with water once step (b) is completed;
(d) eluting said first reverse phase SPE cartridge with acetonitrile or tetrahydrofuran;
(e) directly passing the eluate resulting from said eluting step (d) through a normal phase SPE cartridge to give an acetonitrile or tetrahydrofuran solution comprising purified [18F]flutemetamol;
(f) diluting said acetonitrile or tetrahydrofuran solution comprising purified [18F]flutemetamol with water to form a diluted water/acetonitrile or water/tetrahydrofuran solution comprising purified [18F]flutemetamol, wherein said water/acetonitrile or said water/tetrahydrofuran solution contains about 40-70% (v/v) water;
(g) passing the diluted water/acetonitrile or said diluted water/tetrahydrofuran solution comprising purified [18F]flutemetamol of step (f) through a second reverse phase SPE cartridge and trapping the [18F]flutemetamol on said second reverse phase SPE cartridge;
(h) rinsing said second reverse phase SPE cartridge with water; and
(i) eluting the trapped purified [18F]flutemetamol from second reverse phase SPE cartridge with an injectable organic solvent wherein said injectable organic solvent is ethanol or dimethyl sulfoxide (DMSO).
2. The purification process according to claim 1 , wherein said first reverse phase SPE cartridge of step (b) is washed with a water/acetonitrile mixture.
3. The purification process according to claim 1 , wherein said water/acetonitrile mixture of step (f) contains at least about 50% (v/v) water.
4. The purification process according to claim 1 , wherein said trapped purified [18F]flutemetamol of step (i) is eluted with ethanol.
5. The purification process of claim 1 , wherein:
(i) said first reverse phase SPE cartridge of step (b) is washed with a water/acetonitrile mixture;
(ii) said water/acetonitrile mixture of step (f) contains at least about 50% (v/v) water; and
(iii) said trapped purified [18F]flutemetamol of step (i) is eluted with ethanol.
6. The purification process according to claim 5 , wherein said process is automated.
7. The purification process according to claim 1 wherein said first reverse phase SPE cartridge and said second reverse phase SPE cartridge are each a C30 SPE cartridge.
8. The purification process according to claim 7 , wherein:
(i) said first reverse phase SPE cartridge of step (b) is washed with a water/acetonitrile mixture;
(ii) said water/acetonitrile mixture of step (f) contains at least about 50% (v/v) water; and
(iii) said trapped purified [18F]flutemetamol of step (i) is eluted with ethanol.
9. The purification process according to claim 8 , wherein said process is automated.
10. The purification process according to claim 1 wherein said first reverse phase SPE cartridge and said second reverse phase SPE cartridge are each pre-conditioned with acetonitrile and water.
11. The purification process according to claim 1 wherein said diluting step (f) is performed until said diluted water/acetonitrile mixture comprising purified [18F]flutemetamol contains less than 50% acetonitrile.
12. The purification process according to claim 1 , wherein said process is automated.