Synthesis and biological evaluation of technetium(III) mixed-ligand complexes with high affinity for the cerebral 5-HT(1A) receptor and the alpha1-adrenergic receptor

A Drews; H-J Pietzsch; R Syhre; S Seifert; K Varnäs; H Hall; C Halldin; W Kraus; P Karlsson; C Johnsson; H Spies; B Johannsen

doi:10.1016/s0969-8051(02)00296-2

Synthesis and biological evaluation of technetium(III) mixed-ligand complexes with high affinity for the cerebral 5-HT(1A) receptor and the alpha1-adrenergic receptor

Nucl Med Biol. 2002 May;29(4):389-98. doi: 10.1016/s0969-8051(02)00296-2.

Authors

A Drews¹, H-J Pietzsch, R Syhre, S Seifert, K Varnäs, H Hall, C Halldin, W Kraus, P Karlsson, C Johnsson, H Spies, B Johannsen

Affiliation

¹ Forschungszentrum Rossendorf, Institut für Bioanorganische und Radiopharmazeutische Chemie, Dresden, Germany.

PMID: 12031873
DOI: 10.1016/s0969-8051(02)00296-2

Abstract

Tc(III) and Re(III) complexes [M(NS(3))(CNR)] (M = Re, 99mTc, NS(3) = 2,2',2"-nitrilotris(ethanethiol), CNR = functionalized isocyanide bearing a derivative of WAY 100635) have been synthesized and characterized. Re was used as Tc surrogate for chemical characterization and in vitro receptor-binding studies. For two representatives subnanomolar affinities for the 5-HT(1A) as well as for the alpha1-adrenergic receptor were reached. Biodistribution studies in rats of the 99mTc complexes showed brain uptakes between 0.3 and 0.5% ID/organ (5 min p.i.). In vitro autoradiography of one 99mTc representative in sections of post mortem human brain indicate its accumulation in 5-HT(1A) receptor-rich brain regions. However, addition of the specific 5-HT(1A) receptor agonist 8-OH-DPAT as well as the alpha1-adrenoceptor antagonist prazosin could not substantially block this tracer accumulation. A preliminary SPET study in a monkey showed negligible brain uptake.

Publication types

Comparative Study
Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoradiography
Brain / diagnostic imaging*
Brain / metabolism*
Cadaver
Haplorhini
Humans
In Vitro Techniques
Male
Models, Molecular
Piperazines / chemical synthesis
Piperazines / pharmacokinetics*
Pyridines / chemical synthesis
Pyridines / pharmacokinetics*
Radioisotopes / pharmacokinetics
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / pharmacokinetics
Rats
Rats, Inbred WF
Receptors, Adrenergic, alpha-1 / metabolism*
Receptors, Serotonin / metabolism*
Receptors, Serotonin, 5-HT1
Reproducibility of Results
Rhenium / pharmacokinetics
Sensitivity and Specificity
Technetium / pharmacokinetics*
Tissue Distribution
Tomography, Emission-Computed, Single-Photon

Substances

Piperazines
Pyridines
Radioisotopes
Radiopharmaceuticals
Receptors, Adrenergic, alpha-1
Receptors, Serotonin
Receptors, Serotonin, 5-HT1
N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
Rhenium
Technetium