title: Automation of [(18) F]fluoroacetaldehyde synthesis: application to a recombinant human interleukin-1 receptor antagonist (rhIL-1RA).
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.
authors.affiliation: Wolfson Molecular Imaging Centre, CRUK and EPSRC Cancer Imaging Centre in Cambridge and Manchester, The University of Manchester, Manchester, UK.
authors.forename: Olivia
authors.initials: O
authors.lastname: Morris
authors.affiliation: Wolfson Molecular Imaging Centre, CRUK and EPSRC Cancer Imaging Centre in Cambridge and Manchester, The University of Manchester, Manchester, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: McMahon
authors.affiliation: Wolfson Molecular Imaging Centre, CRUK and EPSRC Cancer Imaging Centre in Cambridge and Manchester, The University of Manchester, Manchester, UK.
authors.forename: Herve
authors.initials: H
authors.lastname: Boutin
authors.affiliation: GE Healthcare, Life Sciences, Imaging R&D, The Grove Centre, Amersham, Bucks, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Grigg
authors.affiliation: Wolfson Molecular Imaging Centre, CRUK and EPSRC Cancer Imaging Centre in Cambridge and Manchester, The University of Manchester, Manchester, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Prenant
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000478:Alkylation; D000818:Animals; D001331:Automation; D060326:Chemistry Techniques, Synthetic; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D005462:Fluorine Radioisotopes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism*; D007553:Isotope Labeling; D051379:Mice; D049268:Positron-Emission Tomography; D011854:Radiochemistry / Q000379:methods*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011994:Recombinant Proteins; C075898:fluoroacetaldehyde; D000079:Acetaldehyde; D004121:Dimethyl Sulfoxide
keywords: PET; [18F]fluoroacetaldehyde; [18F]rhIL1RA; prosthetic group; protein radiolabelling