title: A boronate-caged [¹⁸F]FLT probe for hydrogen peroxide detection using positron emission tomography.
abstract: Reactive oxygen species (ROS) play important roles in the development and progression of cancer and other diseases, motivating the development of translatable technologies for biological ROS imaging. Here we report Peroxy-Caged-[(18)F]Fluorodeoxy thymidine-1 (PC-FLT-1), an oxidatively immolative positron emission tomography (PET) probe for H2O2 detection. PC-FLT-1 reacts with H2O2 to generate [(18)F]FLT, allowing its peroxide-dependent uptake and retention in proliferating cells. The relative uptake of PC-FLT-1 was evaluated using H2O2-treated UOK262 renal carcinoma cells and a paraquat-induced oxidative stress cell model, demonstrating ROS-dependent tracer accumulation. The data suggest that PC-FLT-1 possesses promising characteristics for translatable ROS detection and provide a general approach to PET imaging that can be expanded to the in vivo study of other biologically relevant analytes.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California , San Francisco, California 94158, United States.
authors.forename: Valerie
authors.initials: V
authors.lastname: Carroll
authors.forename: Brian W
authors.initials: BW
authors.lastname: Michel
authors.forename: Joseph
authors.initials: J
authors.lastname: Blecha
authors.forename: Henry
authors.initials: H
authors.lastname: VanBrocklin
authors.forename: Kayvan
authors.initials: K
authors.lastname: Keshari
authors.forename: David
authors.initials: D
authors.lastname: Wilson
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chang
mesh_terms: D001692:Biological Transport; D001897:Boronic Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D049268:Positron-Emission Tomography
chemical_list: D001897:Boronic Acids; D015224:Dideoxynucleosides; D006861:Hydrogen Peroxide; C002854:alovudine