title: Synthesis, in vitro pharmacology and biodistribution studies of new PD 156707-derived ET(A) receptor radioligands.
abstract: It is assumed that the regulation of cardiac endothelin (ET) receptor density is abnormal in heart diseases. From that perspective, an ET receptor radioligand is needed to assess ET receptor density in vivo. The nonpeptidyl ET(A) receptor antagonist PD 169390 was labelled with radioiodine to give a putative radioligand for SPECT. Labelling with [125I]iodide and [123I]iodide was accomplished with good to excellent radiochemical yields. The affinities of the nonradioactive reference and those of selected precursor compounds for ET(A) receptors were determined, using [125I]iodine labelled endothelin-1 with mouse ventricular membranes. All employed substances exhibited potent in vitro pharmacological characteristics with Ki values comparable to that of the lead compound PD 156707. Biodistribution studies and scintigraphic imaging experiments in mice, however, showed no significant uptake of the [123I] derivative in the heart.
authors.affiliation: Department of Nuclear Medicine, Albert-Schweitzer-Str. 33, University Hospital Münster, 48149 Münster, Germany. carsten.hoeltke@uni-muenster.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Höltke
authors.forename: Marilyn P
authors.initials: MP
authors.lastname: Law
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Breyholz
authors.forename: Klaus
authors.initials: K
authors.lastname: Kopka
authors.forename: Christoph
authors.initials: C
authors.lastname: Bremer
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.forename: Otmar
authors.initials: O
authors.lastname: Schober
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004149:Dioxoles / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D065130:Endothelin A Receptor Antagonists; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008861:Microsomes / Q000187:drug effects
chemical_list: D004149:Dioxoles; D065130:Endothelin A Receptor Antagonists; D007457:Iodine Radioisotopes; D008024:Ligands; C093321:PD 156707