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

• Published in: Biomacromolecules 2017-01, Vol.18 (1), p.96-102
• Main Authors: Glassner, Mathias, Palmieri, Luca, Monnery, Bryn D, Verbrugghen, Thomas, Deleye, Steven, Stroobants, Sigrid, Staelens, Steven, wyffels, Leonie, Hoogenboom, Richard
• Format: Article
• Language: English
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.6b01392

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 89Zr and 18F. 18F-labeled PEtOx is prepared by the strain-promoted azide–alkyne cycloaddition (SPAAC) of [18F]­fluoroethylazide to bicyclo[6.1.0]­non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. 89Zr-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 [18F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [89Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of 89Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.