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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Azepines / chemical synthesis*
  • Azepines / chemistry
  • Azepines / pharmacokinetics
  • Benzothiazoles / chemical synthesis*
  • Benzothiazoles / chemistry
  • Benzothiazoles / pharmacokinetics
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Fluorine Radioisotopes
  • In Vitro Techniques
  • Liver / diagnostic imaging
  • Liver / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Receptors, sigma / metabolism*
  • Sigma-1 Receptor
  • Tissue Distribution

Substances

  • 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo(d)thiazol-2(3H)-one
  • Azepines
  • Benzothiazoles
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Receptors, sigma