Optimized and Automated Radiosynthesis of 18FDHMT for Translational Imaging of Reactive Oxygen Species with Positron Emission Tomography

摘要

Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these diseases. For the purpose of clinical translation of [¹⁸F]6-(4-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-methyl-5,6-dihydrophenanthridine-3,8-diamine ([¹⁸F]DHMT), a promising ROS PET radiotracer, we first manually optimized the large-scale radiosynthesis conditions and then implemented them in an automated synthesis module. Our manual synthesis procedure afforded [¹⁸F]DHMT in 120 min with overall radiochemical yield (RCY) of 31.6% ± 9.3% (n = 2, decay-uncorrected) and specific activity of 426 ± 272 GBq/µmol (n = 2). Fully automated radiosynthesis of [¹⁸F]DHMT was achieved within 77 min with overall isolated RCY of 6.9% ± 2.8% (n = 7, decay-uncorrected) and specific activity of 155 ± 153 GBq/µmol (n = 7) at the end of synthesis. This study is the first demonstration of producing 2-[¹⁸F]fluoroethyl azide by an automated module, which can be used for a variety of PET tracers through click chemistry. It is also the first time that [¹⁸F]DHMT was successfully tested for PET imaging in a healthy beagle dog.