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

Michelle L James, Bin Shen, Cristina L Zavaleta, Carsten H Nielsen, Christophe Mesangeau, Pradeep K Vuppala, Carmel Chan, Bonnie A Avery, James A Fishback, Rae R Matsumoto, Sanjiv S Gambhir, Christopher R McCurdy, Frederick T Chin

83 Citationer (Scopus)

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.
OriginalsprogEngelsk
TidsskriftJournal of Medicinal Chemistry
Vol/bind55
Udgave nummer19
Sider (fra-til)8272-82
Antal sider11
ISSN0022-2623
DOI
StatusUdgivet - 2012

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