Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University , Krijgslaan 281-S4, 9000 Ghent, Belgium.
Antwerp University Hospital , Department of Nuclear Medicine, Wilrijkstraat 10, B-2650 Edegem, Belgium.
Biomacromolecules. 2017 Jan 9;18(1):96-102. doi: 10.1021/acs.biomac.6b01392. Epub 2016 Dec 2.
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 and F. 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.
聚（2-烷基-2-恶唑啉）（PAOx）在生物医学应用中受到越来越多的关注。因此，深入了解 PAOx 的生物分布情况至关重要。我们报告了摩尔质量为 5 kDa 的聚（2-乙基-2-恶唑啉）（PEtOx）的生物分布情况，该聚合物通过[F]氟乙基叠氮化物与双环[6.1.0]壬-4-炔（BCN）功能化的 PEtOx 的应变促进叠氮化物-炔烃环加成（SPAAC）反应进行放射性标记，因为许多常见的标记策略都不适用于 PEtOx。Zr 标记的 PEtOx 使用去铁胺末端基团作为螯合剂制备。与更高摩尔质量的 PEtOx 相比，5 kDa 的 PEtOx 表现出更快的血液清除速度，而肝脏摄取量较低，表明肝脏在 5 kDa PEtOx 的排泄中贡献较小。虽然[F]-PEtOx 从肾脏中快速有效地清除，但在研究过程中，5 kDa [Zr]-Df-PEtOx 不能有效地清除，这很可能是由于 Zr 标记的代谢物在肾小管中而不是聚合物本身被捕获所致，这表明在生物分布研究中选择适当的标记物非常重要。
