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

dc.cclicenceCC-BY-NCen
dc.contributor.authorMorris, O.
dc.contributor.authorElsawy, M.
dc.contributor.authorFairclough, M.
dc.contributor.authorWilliams, K.
dc.contributor.authorMcMahon, A.
dc.contributor.authorGrigg, J.
dc.contributor.authorForster, D.
dc.contributor.authorMiller, A.
dc.contributor.authorSaiani, A.
dc.contributor.authorPrenant, C.
dc.date.acceptance2017-06-14
dc.date.accessioned2020-01-28T15:31:53Z
dc.date.available2020-01-28T15:31:53Z
dc.date.issued2017-06-17
dc.descriptionThe Publisher's final version can be found by following the DOI link. open access articleen
dc.description.abstractPositron 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 fluorescein isothiocyanate (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 postinjection) 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 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.en
dc.exception.reasonopen accessen
dc.exception.ref2021codes254aen
dc.funderMRC (Medical Research Council)en
dc.funder.otherGE Healthcareen
dc.funder.otherCancer Imaging Centre in Cambridge and Manchester (CRUK/EPSRC [C8742/A18097])en
dc.identifier.citationMorris, O., Elsawy, M., Fairclough, M., Williams, K., McMahon, A., Grigg, J., Forster, D., Miller, A., Saiani, A., Prenant, C. (2017) In vivo characterisation of a therapeutically relevant self-assembling 18F- labelled β-sheet forming peptide and its hydrogel using positron emission tomography. Journal of Labelled Compounds and Radiopharmaceuticals, 60 (10), pp. 481-488.en
dc.identifier.doihttps://doi.org/10.1002/jlcr.3534
dc.identifier.urihttps://dora.dmu.ac.uk/handle/2086/19083
dc.language.isoenen
dc.peerreviewedYesen
dc.publisherWileyen
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.subjectPositron emission tomographyen
dc.subjectRadiolabelingen
dc.subjectBioimagingen
dc.subjectNanomaterialsen
dc.subjectHydrogelsen
dc.subjectPeptidesen
dc.subjectSelf-assemblyen
dc.subjectFibersen
dc.subjectBiomaterialsen
dc.titleIn vivo characterisation of a therapeutically relevant self-assembling 18F- labelled β-sheet forming peptide and its hydrogel using positron emission tomographyen
dc.typeArticleen

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