title: μPET imaging of the pharmacokinetic behavior of medium and high molar mass (89)Zr-labeled poly(2-ethyl-2-oxazoline) in comparison to poly(ethylene glycol).
abstract: Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile alternative to poly(ethylene glycol)s (PEG). In this work, the pharmacokinetic behavior of well defined (89)Zr-labeled poly(2-ethyl-2-oxazoline)s (PEtOx) was evaluated and compared to that of (89)Zr-labeled PEG, both with varying molar mass. Amine-terminated PEtOx of low dispersity in a molar mass range of 20 to 110kDa and PEG of 20 and 40kDa were functionalized with a desferrioxamine chelator and radiolabeled with (89)Zr. The tissue distribution of both radiolabeled PEtOx and PEG polymers was studied by means of micro Positron Emission Tomography (μPET) molecular imaging in mice longitudinally up to 1week post injection, followed by ex vivo biodistribution. As previously described for other classes of non-ionic polymers, the blood clearance of PEtOx decreased with molar mass. The cut off for glomerular filtration of PEtOx is likely to be around 40kDa. The head to head comparison of PEG and PEtOx revealed that the biodistribution is mostly dominated by polymer chain length and not polymer molar mass. This study constitutes an important addition to further establishing PEtOx as a promising polymer in biomedical applications.
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Wilrijk, Belgium; Antwerp University Hospital, Department of Nuclear Medicine, Wilrijkstraat 10, B-2650 Edegem, Belgium. Electronic address: leonie.wyffels@uza.be.
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Verbrugghen
authors.affiliation: Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Ghent, Belgium.
authors.forename: Bryn D
authors.initials: BD
authors.lastname: Monnery
authors.affiliation: Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Ghent, Belgium.
authors.forename: Mathias
authors.initials: M
authors.lastname: Glassner
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Wilrijk, Belgium; Antwerp University Hospital, Department of Nuclear Medicine, Wilrijkstraat 10, B-2650 Edegem, Belgium.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
authors.affiliation: Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Ghent, Belgium. Electronic address: richard.hoogenboom@ugent.be.
authors.forename: Richard
authors.initials: R
authors.lastname: Hoogenboom
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
mesh_terms: D000818:Animals; D003676:Deferoxamine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D017879:Isothiocyanates / Q000737:chemistry; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009206:Myocardium / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D011868:Radioisotopes; D017262:Siderophores / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015040:Zirconium
chemical_list: C000594275:1,4-phenylene diisothiocyanate; D017879:Isothiocyanates; D011073:Polyamines; D011868:Radioisotopes; D017262:Siderophores; C511916:poly(2-ethyl-2-oxazoline); D011092:Polyethylene Glycols; D015040:Zirconium; D003676:Deferoxamine
keywords: Poly(2-oxazoline); Poly(ethylene glycol); Positron emission tomography