title: Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1.
abstract: Design, radiosynthesis, and biological evaluation of two radiotracers (N-(3-[(18)F]fluoropropyl)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide ((18)F-FPPPT) and (N-(4-[(18)F]fluoroaniline)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide ((18)F-FAPPT)) are described for noninvasive assessment of stearoyl-CoA desaturase-1 (SCD-1). The overexpression of SCD-1 in multiple solid tumors associates with poor survival in cancer patients. The two radiotracers, (18)F-FPPPT and (18)F-FAPPT, were each prepared in three steps in radiochemical yields of 21% and 3%, respectively. The practicality of imaging SCD-1 with (18)F-FPPPT was tested in two mouse models bearing xenograft tumors with different levels of SCD-1 expression, which afforded a 1.8-fold uptake difference correspondingly. Our work indicates that it is possible to develop SCD-1 specific imaging probes from previously reported SCD-1 inhibitors.
authors.affiliation: Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Silvers
authors.affiliation: Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Hancheng
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Orhan K
authors.initials: OK
authors.lastname: Öz
authors.affiliation: Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Xiankai
authors.initials: X
authors.lastname: Sun
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009369:Neoplasms / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D000577:Amides; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D013230:Stearoyl-CoA Desaturase
keywords: (18)F-FPPPT; De novo lipid metabolism; PET; Radiosynthesis; Stearoyl-CoA desaturase