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

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-89 and F-18. F-18-labeled PEtOx is prepared by the strain-promoted azide-alkyne cycloaddition (SPAAC) of [F-18]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-89-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-18]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [Zr-89]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of Zr-89-labeled metabolites in the renal tubules and not the polymer itself, demonstrating,the importance of selecting the appropriate label for biodistribution studies.