Preparation and biodistribution of copper-67 complexes with tetradentate Schiff-base ligands.
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.
John
E K
EK
Department of Medicinal Chemistry, School of Pharmacy, Purdue University, West Lafayette, IN 47907-1333.
Bott
A J
AJ
Green
M A
MA
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D003301:Copper Radioisotopes / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D007668:Kidney / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012545:Schiff Bases; D014018:Tissue Distribution
D003301:Copper Radioisotopes; D008024:Ligands; D009942:Organometallic Compounds; D012545:Schiff Bases