title: Radiosynthesis andin vivoevaluation of a novel σ1selective PET ligand.
abstract: The σ1receptor is an important target for CNS disorders. We previously identified a σ1ligand TZ3108 having highly potent (Ki-σ1= 0.48 nM) and selective affinity for σ1versus σ2receptors. TZ3108 was18F-labeled with F-18 forin vivoevaluation. Biodistribution and blocking studies of [18F]TZ3108 in male Sprague-Dawley rats demonstrated high brain uptake, which was σ1-specific with noin vivodefluorination. MicroPET studies in cynomolgus macaques showed high brain penetration of [18F]TZ3108; the regional brain distribution was consistent with that of the σ1receptor. Pseudo-equilibrium in the brain was reached ~ 45 min post-injection. Metabolite analysis of [18F]TZ3108 in NHP blood and rodent blood and brain revealed that ~ 70% parent remained in the plasma of NHPs 60 min post-injection and the major radiometabolite did not cross the blood-brain barrier in rats. In summary, the potent, selective and metabolically stable σ1specific radioligand [18F]TZ3108 represents a potentially useful PET radioligand for quantifying the σ1receptor in the brain.
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Jinda
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Hubert P
authors.initials: HP
authors.lastname: Flores
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA. ; Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Parsons
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu