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J Med Chem. 2012 Oct 11;55(19):8272-8282. doi: 10.1021/jm300371c. Epub 2012 Sep 20.

New positron emission tomography (PET) radioligand for imaging σ-1 receptors in living subjects.

Author information

1
Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Palo Alto CA 94305-5484, USA.
2
Cluster for Molecular Imaging & Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Denmark.
3
Department of Medicinal Chemistry, The University of Mississippi, University, MS 38677-1848, USA.
4
Department of Pharmaceutics, The University of Mississippi, University, MS 38677-1848, USA.
5
Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University Morgantown, WV 26506-9500, USA.
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Contributed equally

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.

PMID:
22853801
PMCID:
PMC4106900
DOI:
10.1021/jm300371c
[Indexed for MEDLINE]
Free PMC Article

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