Preparation and biodistribution of copper-67 complexes with tetradentate Schiff-base ligands

J Pharm Sci. 1994 Apr;83(4):587-90. doi: 10.1002/jps.2600830429.

Abstract

Uncharged, lipophilic, low molecular weight copper complexes labeled with generator-produced copper-62 are of interest as potential radiopharmaceutials for imaging the brain with positron emission tomography (PET). We report here the synthesis and biodistribution of a series of [67Cu]copper(II) complexes with tetradentate N2O2(2-)Schiff-base ligands. The compounds studied varied in lipophilicity from log P = 1.7 to log P = 3.6, where P is the octanol/water partition coefficient. In rat biodistribution studies the tracers were generally found to penetrate the blood-brain barrier following intravenous injection, but some far better than others. For closely related compounds brain uptake at 1 min postinjection increased with increasing lipophilicity, although log P was clearly not the sole determinant of high brain uptake. Substantial variations were also observed in the rate at which these various compounds are cleared from brain, with a few exhibiting the prolonged cerebral retention of tracer that would be desired for imaging with 62Cu and PET.

Publication types

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

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, Thin Layer
  • Copper Radioisotopes / pharmacokinetics*
  • Isotope Labeling
  • Kidney / metabolism
  • Ligands
  • Liver / metabolism
  • Lung / metabolism
  • Male
  • Myocardium / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Schiff Bases
  • Tissue Distribution

Substances

  • Copper Radioisotopes
  • Ligands
  • Organometallic Compounds
  • Schiff Bases