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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
Author(s) -
Morris O.,
Elsawy M.A.,
Fairclough M.,
Williams K.J.,
Mcmahon A.,
Grigg J.,
Forster D.,
Miller A.F.,
Saiani A.,
Prenant C.
Publication year - 2017
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3534
Subject(s) - chemistry , biodistribution , in vivo , positron emission tomography , excretion , fluorescein isothiocyanate , peptide , nuclear medicine , fluorescence , in vitro , biochemistry , medicine , biology , physics , microbiology and biotechnology , quantum mechanics
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.