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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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 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.

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