Novel oxorhenium and oxotechnetium MO(NS)(S)2 complexes in the development of 5-HT1A receptor imaging agents

J Inorg Biochem. 2003 Jan 15;93(3-4):213-20. doi: 10.1016/s0162-0134(02)00574-3.

Abstract

The [NS][S](2) mixed-ligand system was applied to synthesize oxorhenium and oxotechnetium complexes of the general formula MO(o-CH(3)OC(6)H(4)N(CH(2)CH(2))(2)NCH(2)CH(2)S)(p-CH(3)C(6)H(4)S)(2) (M=Re in 1, M=(99)Tc in 2, and M=(99m)Tc in 3). The bidentate [NS] ligand includes the 1-(2-methoxyphenyl)piperazine moiety which is a fragment of the true 5-HT(1A) antagonist WAY 100635. The oxorhenium complex 1 was prepared by a ligand exchange reaction using ReOCl(3)(PPh(3))(2) as precursor while [Bu(4)N][(99)TcOCl(4)] and (99)Tc-gluconate were used as precursors in the synthesis of the oxotechnetium-99 complex 2. Both complexes were characterized by elemental analysis and spectroscopic methods. Crystallographic analysis of 1 showed that the rhenium coordination geometry is trigonal bipyramidal. The basal plane of the trigonal bipyramid is defined by the oxo group and two sulphur atoms, one belonging to the [NS] ligand and the other to an aromatic thiol, while the apical positions are occupied by the nitrogen of the [NS] ligand and the sulphur of the second aromatic thiol. The oxotechnetium-99 complex 2 has almost identical unit cell parameters to those of the oxorhenium complex 1 indicating, in combination with the other analytical data, that the complexes are isostructural. The binding affinity of the oxorhenium complex 1 for the 5-HT(1A) receptor subtype was determined in rat brain hippocampal preparations (IC(50)=106 nM). The oxotechnetium-99m complex 3 was prepared by a ligand exchange reaction using (99m)Tc-glucoheptonate as the precursor. Its structure was established by comparative HPLC studies using the oxotechnetium-99 complex 2 as a reference. Complex 3 was administered by intravenous injection in rats. At 2 min post injection, 0.153% of the injected dose per gram of tissue was measured in rat brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media
  • Crystallography, X-Ray
  • Diagnostic Imaging / methods
  • Hippocampus / chemistry
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism
  • Ligands
  • Male
  • Molecular Structure
  • Organometallic Compounds* / administration & dosage
  • Organometallic Compounds* / pharmacokinetics
  • Radioisotopes / administration & dosage
  • Radionuclide Imaging
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / analysis*
  • Receptors, Serotonin, 5-HT1
  • Rhenium* / administration & dosage
  • Rhenium* / pharmacokinetics
  • Technetium* / administration & dosage
  • Technetium* / pharmacokinetics
  • Tissue Distribution

Substances

  • Contrast Media
  • Ligands
  • Organometallic Compounds
  • Radioisotopes
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Rhenium
  • Technetium