Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1

Bioorg Med Chem Lett. 2016 Feb 1;26(3):924-927. doi: 10.1016/j.bmcl.2015.12.062. Epub 2015 Dec 19.

Abstract

Design, radiosynthesis, and biological evaluation of two radiotracers (N-(3-[(18)F]fluoropropyl)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide ((18)F-FPPPT) and (N-(4-[(18)F]fluoroaniline)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide ((18)F-FAPPT)) are described for noninvasive assessment of stearoyl-CoA desaturase-1 (SCD-1). The overexpression of SCD-1 in multiple solid tumors associates with poor survival in cancer patients. The two radiotracers, (18)F-FPPPT and (18)F-FAPPT, were each prepared in three steps in radiochemical yields of 21% and 3%, respectively. The practicality of imaging SCD-1 with (18)F-FPPPT was tested in two mouse models bearing xenograft tumors with different levels of SCD-1 expression, which afforded a 1.8-fold uptake difference correspondingly. Our work indicates that it is possible to develop SCD-1 specific imaging probes from previously reported SCD-1 inhibitors.

Keywords: (18)F-FPPPT; De novo lipid metabolism; PET; Radiosynthesis; Stearoyl-CoA desaturase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Animals
  • Cell Line, Tumor
  • Drug Design*
  • Fluorine Radioisotopes / chemistry
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasms / diagnostic imaging
  • Positron-Emission Tomography
  • Radiography
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Stearoyl-CoA Desaturase / antagonists & inhibitors
  • Stearoyl-CoA Desaturase / metabolism*
  • Transplantation, Heterologous

Substances

  • Amides
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Stearoyl-CoA Desaturase