In vivo characterisation of a therapeutically relevant self-assembling 18F-labelled [beta]-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 si...

Full description

Saved in:
Bibliographic Details
Published in:Journal of labelled compounds & radiopharmaceuticals 2017-08, Vol.60 (10), p.481
Main Authors: Morris, O, Elsawy, MA, Fairclough, M, Williams, KJ, Mcmahon, A, Grigg, J, ster, D, Miller, AF, Saiani, A, Prenant, C
Format: Article
Language:English
Subjects:
Assembling
Bladder
Disaggregation
Emission analysis
Excretion
Fluorescein
Fluorescein isothiocyanate
Fluorescence
Forming
Fragments
Hydrogels
Injection
Intravenous administration
Kidneys
Labeling
Mice
Pharmacokinetics
Pharmacology
Positron emission
Positron emission tomography
Renal function
Rodents
Stability analysis
Tomography
Urinary bladder
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0362-4803
1099-1344
DOI:10.1002/jlcr.3534