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In vivo characterisation of a therapeutically relevant self-assembling (18) F-labelled β-sheet forming peptide and its hydrogel using positron emission tomography.Morris, Olivia C; Elsawy, M; Fairclough, M; Williams, Kaye J; McMahon, Adam; Grigg, J; Forster, Duncan; Miller, A; Saiani, A; Prenant, Christian; et al. (2017-08)Positron emission tomography (PET) and fluorescence labelling have been used to assess the pharmacokinetics, biodistribution and eventual fate of a hydrogel-forming nonapeptide, FEFKFEFKK (F9), in healthy mice, using (18) F-labelled and fluorescein isothiocyanate (FITC)-labelled F9 analogues. F9 was site-specifically radiolabelled with 2-[(18) F]fluoro-3-pyridinecarboxaldehyde ([(18) F]FPCA) via oxime bond formation. [(18) F]FPCA-F9 in vivo fate was evaluated both as a solution, following intravenous administration, and as a hydrogel when subcutaneously injected. The behaviour of FITC-F9 hydrogel was assessed following subcutaneous injection. [(18) F]FPCA-F9 demonstrated high plasma stability and primarily renal excretion; [(18) F]FPCA-F9 when in solution and injected into the bloodstream displayed prompt bladder uptake (53.4 ± 16.6 SUV at 20 minutes postinjection) and rapid renal excretion, whereas [(18) F]FPCA-F9 hydrogel, formed by co-assembly of [(18) F]FPCA-F9 monomer with unfunctionalised F9 peptide and injected subcutaneously, showed gradual bladder accumulation of hydrogel fragments (3.8 ± 0.4 SUV at 20 minutes postinjection), resulting in slower renal excretion. Gradual disaggregation of the F9 hydrogel from the site of injection was monitored using FITC-F9 hydrogel in healthy mice (60 ± 3 over 96 hours), indicating a biological half-life between 1 and 4 days. The in vivo characterisation of F9, both as a gel and a solution, highlights its potential as a biomaterial.
A review of approaches to 18 F radiolabelling affinity peptides and proteins.Morris, Olivia C; Fairclough, M; Grigg, J; Prenant, Christian; McMahon, Adam; Wolfson Molecular Imaging Centre, The University of Manchester, UKCRUK/EPSRC Imaging Centre in Cambridge & Manchester, The University of Manchester, UKWolfson Molecular Imaging Centre, The University of Manchester, UK (2018-05-08)Affinity peptide and protein- (APP) based radiotracers are an increasingly popular class of radiotracer in positron emission tomography (PET), which was once dominated by the use of small molecule radiotracers. Radiolabelled monoclonal antibodies (mAbs) are important examples of APPs, yet a preference for smaller APPs, which exhibit fast pharmacokinetics and permit rapid PET aided diagnosis, has become apparent. 18 F exhibits favourable physical characteristics for APP radiolabelling and has been described as an ideal PET radionuclide. Notwithstanding, 18 F radiolabelling of APP is challenging, and this is echoed in the literature where a number of diverse approaches have been adopted. This review seeks to assess and compare the approaches taken to 18 F APP radiolabelling with the intention of highlighting trends within this expanding field. Generic themes have emerged in the literature, namely the use of mild radiolabelling conditions, a preference of site-specific methodologies with an impetus for short, automated procedures which produce high-yielding [18 F]APPs.