Synthesis and evaluation of [123I]-iodo-PK11195 for mapping peripheral-type benzodiazepine receptors (omega 3) in heart

Nucl Med Biol. 1996 Jan;23(1):23-8. doi: 10.1016/0969-8051(95)02007-1.

Abstract

An iodinated analog of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxamide , a specific antagonist of the peripheral-type benzodiazepine receptor (omega 3), has been synthesized in three steps with an overall chemical yield of 40%. Both [123I]- and [125I]-Iodo-PK11195 have been synthesized by solid-state isotopic exchange in > 60% isolated radiochemical yield and specific activity of 233-348 mCi/mmol. Tissue distribution studies in rats indicate a high uptake of radioactivity in adrenal glands, heart, lung and kidneys, which was blocked 63-87% by preadministration of cold PK11195. Single photon emission computer tomography (SPECT) imaging of the canine heart has been accomplished with [123I]PK11195. These results suggest that [123I]PK11195 has potential as a SPECT radiotracer for studying the omega 3 receptor in humans.

Publication types

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

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Dogs
  • Female
  • Heart / diagnostic imaging*
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Isoquinolines* / chemical synthesis
  • Isoquinolines* / pharmacokinetics
  • Isotope Labeling
  • Male
  • Myocardium / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Iodine Radioisotopes
  • Isoquinolines
  • Receptors, GABA-A
  • PK 11195