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

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 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.