The Label Matters: μPET Imaging of the Biodistribution of Low Molar Mass ⁸⁹Zr and ¹⁸F-Labeled Poly(2-ethyl-2-oxazoline)

Abstract

Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. Therefore, it is of fundamental importance to gain an in-depth understanding of the biodistribution profile of PAOx. We report the biodistribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes Zr andF. F-labeled PEtOx is prepared by the strain-promoted azide-alkyne cycloaddition (SPAAC) of [F]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. Zr-labeled PEtOx is prepared using desferrioxamine end-groups as a chelator. Five kDa PEtOx shows a significantly faster blood clearance compared to PEtOx of higher molar mass while uptake in the liver is lower, indicating a minor contribution of the liver in excretion of the 5 kDa PEtOx. While [F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.

Poly(2‐oxazoline) Hydrogels: State‐of‐the‐Art and Emerging Applications

“…Clearly the same chemistry could be used to create hydrogels with only slight modifications. Likewise, strain‐promoted azide–alkyne cycloaddition is an example of a conjugation tool that has been adapted to create PEG hydrogels and could equally be applied to PAOx with only minor modifications to the previously reported bicyclo[6.1.0]non‐4‐yne terminated PEtOx . Similarly, glyco–PAOx, POxylated–proteins, and PAOx–nucleic acids conjugates that were previously reported have potential to be modified for hydrogel synthesis using physical or covalent cross‐linking.…”

Chain and Step Growth Polymerizations of Cyclic Imino Ethers: From Poly(2‐oxazoline)s to Poly(ester amide)s

“…Wyffels and Hoogenboom introduced the preparation of high molar mass POx with molar masses up to 110 kDa and low dispersities (Đ < 1.11). [30b] In this study, PEtOx (40 kDa) was reported to be an ideal candidate which shows an optimal balance between extended blood circulation time and low non‐specific agglomeration in the body. Moreadith, Viegas and colleagues designed a polymer‐peptide conjugate based on PEtOx and rotigotine for the treatment of Parkinson's disease .…”

Tumor targeting with pH-responsive poly(2-oxazoline)-based nanogels for metronomic doxorubicin treatment

“…Poly(2-oxazoline)s (POx) represent a promising alternative as they are biocompatible, [ 13 , 23 , 24 ] and show a stealth behavior similar to PEG when the side chain substitution is chosen correctly [ 25 , 26 ]. Recent studies elucidate the pharmacokinetic behavior of the polymer dependent on its molar mass, demonstrating superior behavior when compared to PEG [ 27 , 28 ]. The first clinical study using a POx derivative is currently ongoing (SER-214, phase I) [ 14 ] and the polymer was approved by the federal food administration (FDA) as an indirect additive used in food contact substances (21CFR175.105) in 2016.…”