Billaud Emilie M F, Shahbazali Elnaz, Ahamed Muneer, Cleeren Frederik, Noël Timothy, Koole Michel, Verbruggen Alfons, Hessel Volker, Bormans Guy
Laboratory of Radiopharmacy , Department of Pharmaceutical and Pharmacological Sciences , KU Leuven , Campus Gasthuisberg, O&N2, Herestraat 49, Box 821 , 3000 Leuven , Belgium . Email:
Micro Flow Chemistry & Process Technology , Chemical Engineering and Chemistry Department , TU Eindhoven , P. O. Box 513 , 5600 MB Eindhoven , The Netherlands.
Chem Sci. 2017 Feb 1;8(2):1251-1258. doi: 10.1039/c6sc02933g. Epub 2016 Oct 7.
Pretargeted PET imaging has emerged as an effective two-step approach that combines the superior affinity and selectivity of antibodies with the rapid pharmacokinetics and favorable dosimetry of smaller molecules radiolabeled with short-lived radionuclides. This approach can be based on the bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) reaction between tetrazines and -cyclooctene (TCO) derivatives. We aimed to develop new [F]TCO-dienophiles with high reactivity for IEDDA reactions, and favorable stability and pharmacokinetics. New dienophiles were synthesized using an innovative micro-flow photochemistry process, and their reaction kinetics with a tetrazine were determined. stability and biodistribution of the most promising F-radiolabeled-TCO-derivative () was investigated, and its potential for pretargeted PET imaging was assessed in tumor-bearing mice. We demonstrated that is a suitable dienophile for IEDDA reactions and for pretargeting applications.
预靶向正电子发射断层显像（PET）已成为一种有效的两步法，它将抗体的高亲和力和选择性与用短寿命放射性核素标记的小分子的快速药代动力学和良好的剂量学特性相结合。这种方法可以基于四嗪与环辛烯（TCO）衍生物之间的生物正交逆电子需求狄尔斯-阿尔德（IEDDA）反应。我们旨在开发对IEDDA反应具有高反应性、良好稳定性和药代动力学的新型[F]TCO亲双烯体。使用创新的微流光化学工艺合成了新型亲双烯体，并测定了它们与四嗪的反应动力学。研究了最有前景的F放射性标记TCO衍生物（）的稳定性和生物分布，并在荷瘤小鼠中评估了其用于预靶向PET显像的潜力。我们证明是一种适用于IEDDA反应和预靶向应用的亲双烯体。
