Development of 123I-labelled NNC 13-8241 as a radioligand for SPECT visualization of benzodiazepine receptor binding

Nucl Med Biol. 1996 Apr;23(3):201-9. doi: 10.1016/0969-8051(95)02041-1.

Abstract

[125I]- and [123I]NNC 13-8241 were prepared from the trimethyltin precursor and radioactive iodide using the chloramine-T method. The total radiochemical yields of [125I]- and [123I]NNC 13-8241 were 60-70% and 40-50% respectively, with radiochemical purity higher than 98%. In binding studies with [125I]NNC 13-8241 in rats in vitro and in vivo a high uptake of radioactivity was demonstrated in brain regions known to have a high density of benzodiazepine (BZ) receptors such as the occipital and frontal cortex. SPECT examination with [123I]NNC 13-8241 in a Cynomolgus monkey demonstrated a high uptake of radioactivity in the occipital and frontal cortex. After displacement with flumazenil radioactivity in these brain regions was reduced to the level of a central region including the pons. Four hours after injection about 80% of the radioactivity in monkey plasma represented unchanged radioligand. This low degree of metabolism indicates that NNC 13-8241 is metabolically more stable than the radioligands hitherto developed for imaging of BZ-receptors in the primate brain.

Publication types

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

MeSH terms

  • Animals
  • Benzodiazepines / metabolism*
  • Benzodiazepines / pharmacokinetics
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Chromatography, High Pressure Liquid
  • Iodine Radioisotopes* / pharmacokinetics
  • Isotope Labeling / methods
  • Macaca fascicularis
  • Male
  • Radioligand Assay / methods
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / analysis*
  • Receptors, GABA-A / metabolism
  • Tissue Distribution
  • Tomography, Emission-Computed*

Substances

  • Iodine Radioisotopes
  • NNC 13-8241
  • Receptors, GABA-A
  • Benzodiazepines