| Literature DB >> 22853801 |
Michelle L James1, Bin Shen1, Cristina L Zavaleta1, Carsten H Nielsen1,2, Christophe Mesangeau3, Pradeep K Vuppala4, Carmel Chan1, Bonnie A Avery4, James A Fishback5, Rae R Matsumoto5, Sanjiv S Gambhir1, Christopher R McCurdy3, Frederick T Chin1.
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.Entities:
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Year: 2012 PMID： 22853801 PMCID： PMC4106900 DOI： 10.1021/jm300371c
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446