Radiolabelled compounds have uses in medical imaging and, in the case of 18F radiolabelled compounds, in Positron Emission Tomography (PET).
One family of radiolabelled compounds of particular, current interest are radiolabelled thymidines and, in particular, 3′-deoxy-3′-[18F] fluorothymidine (18FLT) for PET imaging especially in the field of oncology.
18FLT may be synthesized from 5′-O-(4′,4′-dimethoxytrityl) thymidine by nucleophilic substitution (with inversion of stereo chemistry) at the 3′ position using 18F as illustrated in scheme 1.

During this fluorination procedure, the elimination product d4T is often formed in high yield owing to competition between OH− and 18F− and is therefore the main impurity in this reaction. d4T tends to be formed at a much higher rate than 18FLT and may be present in a d4T:18FLT ratio of 100-10000:1. Separation of 18FLT and d4T may be problematic.
High performance liquid chromatographic separation of the two compounds may be achieved using different stationary phases, however HPLC is costly and complex and not a preferred purification method in a clinical environment such as a hospital.
HPLC methods can also be time consuming which is a particular problem with the use of radionuclides with short half lives (18F has a half-life of about 110 minutes). Another serious problem is that HPLC does not lend itself to use with commercially available synthesis modules which simplify the preparation and purification of radiolabelled compounds.
WO 2005/025519 describes a method and apparatus for the automated synthesis of 18FLT in which a separation procedure is performed using a Sep-Pak® C-18 solid phase extraction (SPE) column.
WO 2006/133732 also describes a method for the manufacture of [18F]-FLT in which a separation is performed using an Oasis® HLB SPE column.
Unfortunately, the SPE methods previously described for use in the manufacture of [18F]-FLT do not result in good enough separation and so are not always suitable for clinical use.
The present invention aims to address the problems mentioned above by providing a separation process which is relatively simple, less costly than HPLC, results in excellent separation and lends itself to use, especially, in a clinical environment.