Fluorine-18-labeled benzamide analogues for imaging the sigma2 receptor status of solid tumors with positron emission tomography

J Med Chem. 2007 Jul 12;50(14):3194-204. doi: 10.1021/jm0614883. Epub 2007 Jun 19.

Abstract

A series of fluorine-containing benzamide analogs was synthesized and evaluated as candidate ligands for positron emission tomography (PET) imaging of the sigma-2 (sigma2) receptor status of solid tumors. Four compounds having a moderate to high affinity for sigma2 receptors and a moderate to low affinity for sigma-1 (sigma1) receptors were radiolabeled with fluorine-18 via displacement of the corresponding mesylate precursor with [18F]fluoride. Biodistribution studies in female Balb/c mice bearing EMT-6 tumor allografts demonstrated that all four F-18-labeled compounds had a high tumor uptake (2.5-3.7% ID/g) and acceptable tumor/normal tissue ratios at 1 and 2 h post-i.v. injection. An analysis of the chemistry and biodistribution data suggested that N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-[18F]-fluoroethoxy)-5-methylbenzamide ([18F]3c) and N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-[18F]-fluoroethoxy)-5-iodo-3-methoxybenzamide ([18F]3f) are acceptable compounds for imaging the sigma2 receptor status of solid tumors.

Publication types

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

MeSH terms

  • Animals
  • Benzamides* / chemistry
  • Benzamides* / pharmacokinetics
  • Brain / metabolism
  • Female
  • Fluorine Radioisotopes / chemistry*
  • Guinea Pigs
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / diagnostic imaging*
  • Neoplasms / metabolism
  • Positron-Emission Tomography
  • Receptors, sigma / metabolism*
  • Tissue Distribution

Substances

  • Benzamides
  • Fluorine Radioisotopes
  • Receptors, sigma