title: PET-compatible endothelin receptor radioligands: synthesis and first in vitro and in vivo studies.
abstract: The expression and function of endothelin (ET) receptors is abnormal in cardiovascular diseases, tumor progression, and tumor metastasis. In this study, we prepared two [(18)F]-fluorinated derivatives of the non-peptide ET(A) receptor antagonist PD 156707 and evaluated their ET receptor binding potencies. Ex vivo as well as in vivo biodistribution studies in mice were performed, as well as the metabolism of the radiotracer, which was examined by metabolite analysis in mice and rats. All tested derivatives of PD 156707 exhibited potent in vitro pharmacological characteristics with K(i) values comparable to that of the lead compound. The biodistribution studies showed a high accumulation of the tracer in bile and intestine. In vivo we were able to show that the visualization of the heart as a major target organ with high ET(A)R expression is possible.
authors.affiliation: Department of Nuclear Medicine, Albert-Schweitzer-Str. 33, University Hospital Münster, D-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: Klaus
authors.initials: K
authors.lastname: Kopka
authors.forename: Andreas
authors.initials: A
authors.lastname: Faust
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Breyholz
authors.forename: Otmar
authors.initials: O
authors.lastname: Schober
authors.forename: Christoph
authors.initials: C
authors.lastname: Bremer
authors.forename: Burkhard
authors.initials: B
authors.lastname: Riemann
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
mesh_terms: D000818:Animals; D004149:Dioxoles / Q000493:pharmacokinetics / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D049268:Positron-Emission Tomography; D051381:Rats; D017466:Receptors, Endothelin / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004149:Dioxoles; D065128:Endothelin Receptor Antagonists; D008024:Ligands; C093321:PD 156707; D017466:Receptors, Endothelin