Automation of [18F]fluoroacetaldehyde synthesis: application to a recombinant human interleukin‐1 receptor antagonist (rhIL‐1RA). (6th April 2016)

• Record Type: Journal Article
• Authors: Morris, Olivia; McMahon, Adam; Boutin, Herve; Grigg, Julian; Prenant, Christian
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 59:Number 7(2016)
• Page Start: 277
• Page End: 283
• Publication Date: 2016-04-06
• Subjects: [18F]fluoroacetaldehyde -- [18F]rhIL1RA -- protein radiolabelling -- prosthetic group -- PET; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3393
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : [ 18 F]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 [ 18 F]fluoride whilst minimising radiochemist exposure and enhancing reproducibility. In order to achieve full‐automation of [ 18 F]fluoroacetaldehyde peptide radiolabelling, a customised GE Tracerlab FX‐FN with fully programmed automated synthesis was developed. The automated synthesis of [ 18 F]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 [ 18 F]fluoroacetaldehyde was achieved within 2 h. Radiolabelling efficiency of rhIL‐1RA with [ 18 F]fluoroacetaldehyde was confirmed using HPLC and reached 20% ± 10 ( n = 5). Overall RCY of [ 18 F]rhIL‐1RA was 5% ± 2 (decay‐corrected, n = 5) within 2 h starting from 35 to 40 GBq of [ 18 F]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 [ 18 F]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. Abstract : Radiosynthesis of the biocompatible prosthetic group [ 18 F]fluoroacetaldehyde has been fully automated using a customised GE Tracerlab FX‐FN. The configuration achieves comparable [ 18 F]fluoroacetaldehyde RCY to a semi‐automated setup that is limited to smaller quantities of [ 18 F]fluoride. The platform has also been further adapted to permit automated radiolabelling of a recombinant human interleukin‐1 receptor antagonist with [ 18 F]fluoroacetaldehyde. The current work demonstrates the applicability of [ 18 F]fluoroacetaldehyde in peptide and protein radiolabelling, and its automation exhibits its progression potential from pre‐clinical to clinical production.