Automation of [18F]fluoroacetaldehyde synthesis: application to a recombinant human interleukin-1 receptor antagonist (rhIL-1RA)

[18F]Fluoroacetaldehyde is a biocompatible prosthetic group that has been implemented pre-clinically using a semi-automated remotely controlled system. Automation of radiosyntheses permits use of higher levels of [18F]fluoride whilst minimising radiochemist exposure and enhancing reproducibility. In order to achieve full-automation of [18F]fluoroacetaldehyde peptide radiolabelling, a customised GE Tracerlab FX-FN with fully programmed automated synthesis was developed.
The automated synthesis of [18F]fluoroacetaldehyde is carried out using a commercially available precursor, with reproducible yields of 26% ± 3 (decay-corrected, n = 10) within 45 min. Fully automated radiolabelling of a protein, recombinant human interleukin-1 receptor antagonist (rhIL-1RA), with [18F]fluoroacetaldehyde was achieved within 2 h. Radiolabelling efficiency of rhIL-1RA with [18F]fluoroacetaldehyde was confirmed using HPLC and reached 20% ± 10 (n = 5).

Overall RCY of [18F]rhIL-1RA was 5% ± 2 (decay-corrected, n = 5) within 2 h starting from 35 to 40 GBq of [18F]fluoride. Specific activity measurements of 8.11–13.5 GBq/µmol were attained (n = 5), a near three-fold improvement of those achieved using the semi-automated approach.

The strategy can be applied to radiolabelling a range of peptides and proteins with [18F]fluoroacetaldehyde analogous to other aldehyde-bearing prosthetic groups, yet automation of the method provides reproducibility thereby aiding translation to Good Manufacturing Practice manufacture and the transformation from pre-clinical to clinical production.