In vivo characterisation of a therapeutically relevant self-assembling 18F-labelled β-sheet forming peptide and its hydrogel using positron emission tomography

Olivia Morris, Mohamed Elsawy, Michael Fairclough, Kaye Williams, Adam Mcmahon, J. Grigg, Duncan Forster, A.F. Miller, Aline Saiani, Christian Prenant

Research output: Contribution to journalArticlepeer-review

Abstract

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 18F-labelled and fluoresceinisothiocyanate (FITC) - labelled F9 analogues. F9 was site-specifically radiolabelled with 2-[18F]fluoro-3-pyridinecarboxaldehyde ([18F]FPCA) via oxime bond formation. [18F]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. [18F]FPCA-F9 demonstrated high plasma stability and primarily renal excretion; [18F]FPCA-F9 when in solution and injected into the bloodstream displayed prompt bladder uptake (53.4 ± 16.6 SUV at 20 minutes post injection) and rapid renal excretion, whereas [18F]FPCA-F9 hydrogel, formed by co-assembly of [18F]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 post injection), 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 1-4 days. The in vivo characterisation of F9, both as a gel and a solution highlights its potential as a biomaterial.
Original languageEnglish
Pages (from-to)481-488
Number of pages8
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume60
Issue number10
Early online date17 Jun 2017
DOIs
Publication statusPublished - Aug 2017

Research Beacons, Institutes and Platforms

  • Manchester Institute of Biotechnology

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