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A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Michelle L James
  • Bin Shen
  • Cristina L Zavaleta
  • Nielsen, Carsten Haagen
  • Christophe Mésangeau
  • Pradeep K Vuppala
  • Carmel Chan
  • Bonnie A Avery
  • James A Fishback
  • Rae R Matsumoto
  • Sanjiv S Gambhir
  • Christopher R McCurdy
  • Frederick T Chin
Sigma-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. Pre-treatment with 1 mg/kg haloperidol (2), non-radioactive 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)8272-8282
Antal sider11
ISSN0022-2623
DOI
StatusUdgivet - 2012

ID: 40245966