title: New positron emission tomography (PET) radioligand for imaging σ-1 receptors in living subjects.
abstract: σ-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination, and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([(18)F]FTC-146, [(18)F]13). [(18)F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/μmol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [(18)F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [(18)F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [(18)F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [(18)F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Palo Alto CA 94305-5484, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: James
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Palo Alto CA 94305-5484, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Palo Alto CA 94305-5484, USA.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Zavaleta
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Palo Alto CA 94305-5484, USA.|Cluster for Molecular Imaging & Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Carsten H
authors.initials: CH
authors.lastname: Nielsen
authors.affiliation: Department of Medicinal Chemistry, The University of Mississippi, University, MS 38677-1848, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Mesangeau
authors.affiliation: Department of Pharmaceutics, The University of Mississippi, University, MS 38677-1848, USA.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Vuppala
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Palo Alto CA 94305-5484, USA.
authors.forename: Carmel
authors.initials: C
authors.lastname: Chan
authors.affiliation: Department of Pharmaceutics, The University of Mississippi, University, MS 38677-1848, USA.
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Avery
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University Morgantown, WV 26506-9500, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Fishback
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University Morgantown, WV 26506-9500, USA.
authors.forename: Rae R
authors.initials: RR
authors.lastname: Matsumoto
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Palo Alto CA 94305-5484, USA.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.affiliation: Department of Medicinal Chemistry, The University of Mississippi, University, MS 38677-1848, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McCurdy
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Palo Alto CA 94305-5484, USA.
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
mesh_terms: D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005462:Fluorine Radioisotopes; D066298:In Vitro Techniques; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*; D014018:Tissue Distribution; D000097605:Sigma-1 Receptor
chemical_list: D001381:Azepines; D052160:Benzothiazoles; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C577112:6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo(d)thiazol-2(3H)-one