title: Optimized and Automated Radiosynthesis of [18F]DHMT for Translational Imaging of Reactive Oxygen Species with Positron Emission Tomography.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu 610041, China. wenjie.zhang@yale.edu.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA. zhengxin.cai@yale.edu.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu 610041, China. lilinhuaxi@sina.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA. jim.ropchan@yale.edu.
authors.forename: Jim
authors.initials: J
authors.lastname: Ropchan
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA. keunpoong.lim@yale.edu.
authors.forename: Keunpoong
authors.initials: K
authors.lastname: Lim
authors.affiliation: Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, CT 06520, USA. nabil.boutagy@yale.edu.
authors.forename: Nabil E
authors.initials: NE
authors.lastname: Boutagy
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA. j.wu@yale.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, CT 06520, USA. john.stendahl@yale.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Stendahl
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA. chuw@mir.wustl.edu.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Chu
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA. groplerr@mir.wustl.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Gropler
authors.affiliation: Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, CT 06520, USA. albert.sinusas@yale.edu.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Sinusas
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA. chi.liu@yale.edu.
authors.forename: Chi
authors.initials: C
authors.lastname: Liu
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA. henry.huang@yale.edu.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D004285:Dogs; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D057170:Translational Research, Biomedical
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals
keywords: 2-[18F]fluoroethyl azide; PET; automation; in vivo imaging; reactive oxygen species; translational study