μPET imaging of the pharmacokinetic behavior of medium and high molar mass ⁸⁹Zr-labeled poly(2-ethyl-2-oxazoline) in comparison to poly(ethylene glycol)

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• 作者：Leonie wyffels^a ; ^b ; ¹ ; ^{leonie.wyffels@uza.be" class="auth_mail" title="E-mail the corresponding author} ; Thomas Verbrugghen^a ; ¹ ; Bryn D. Monnery^c ; Mathias Glassner^c ; Sigrid Stroobants^a ; ^b ; Richard Hoogenboom^c ; ^{richard.hoogenboom@ugent.be" class="auth_mail" title="E-mail the corresponding author} ; Steven Staelens^a
• 关键词：Poly(2-oxazoline) ; Poly(ethylene glycol) ; Positron emission tomography
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 August 2016
• 年：2016
• 卷：235
• 期：Complete
• 页码：63-71
• 全文大小：1196 K

文摘

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 ⁸⁹Zr-labeled poly(2-ethyl-2-oxazoline)s (PEtOx) was evaluated and compared to that of ⁸⁹Zr-labeled PEG, both with varying molar mass. Amine-terminated PEtOx of low dispersity in a molar mass range of 20 to 110 kDa and PEG of 20 and 40 kDa were functionalized with a desferrioxamine chelator and radiolabeled with ⁸⁹Zr. 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 1 week 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 40 kDa. 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.