利用F预靶向的IEDDA“点击”化学在活细胞中检测缺氧。

Allott Louis, Chen Cen, Braga Marta, Leung Sau Fung Jacob, Wang Ning, Barnes Chris, Brickute Diana, Carroll Laurence, Aboagye Eric O

Comprehensive Cancer Imaging Centre, Faculty of Medicine, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Du Cane Road London W12 0NN UK

Positron Emission Tomography Research Centre, Faculty of Health Sciences, University of Hull Cottingham Road Kingston upon Hull HU6 7RX UK.

RSC Adv. 2021 Jun 7;11(33):20335-20341. doi: 10.1039/d1ra02482e.

We have exemplified a pretargeted approach to interrogate hypoxia in live cells using radioactive bioorthogonal inverse electron demand Diels-Alder (IEDDA) "click" chemistry. Our novel F-tetrazine probe ([F]FB-Tz) and 2-nitroimidazole-based TCO targeting molecule () showed statistically significant ( < 0.0001) uptake in hypoxic cells ( 90 %ID per mg) normoxic cells (<10 %ID per mg) in a 60 min incubation of [F]FB-Tz. This is the first time that an intracellularly targeted small-molecule for IEDDA "click" has been used in conjunction with a radioactive reporter molecule in live cells and may be a useful tool with far-reaching applicability for a variety of applications.

我们展示了一种预靶向方法，利用放射性生物正交逆电子需求狄尔斯-阿尔德（IEDDA）“点击”化学来研究活细胞中的缺氧情况。我们新型的氟代四嗪探针（[F]FB-Tz）和基于2-硝基咪唑的反式环辛烯靶向分子在[F]FB-Tz孵育60分钟后，在缺氧细胞（每毫克90%注射剂量）中的摄取量与常氧细胞（每毫克<10%注射剂量）相比具有统计学显著差异（<0.0001）。这是首次将用于IEDDA“点击”的细胞内靶向小分子与放射性报告分子结合用于活细胞，并且可能是一种具有广泛适用性的有用工具，可用于多种应用。