Synthesis, in vitro pharmacology and biodistribution studies of new PD 156707-derived ET sub(A) receptor radioligands

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 sub(A) receptor antagonist PD 169390 was labelled with radioiodine to give a putative radioligand for SPECT. Labelling with [ super(125)I]iodide and [ super(123)I]iodide was accomplished with good to excellent radiochemical yields. The affinities of the nonradioactive reference and those of selected precursor compounds for ET sub(A) receptors were determined, using [ super(125)I]iodine labelled endothelin-1 with mouse ventricular membranes. All employed substances exhibited potent in vitro pharmacological characteristics with K sub(i) 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 [ super(123)I] derivative in the heart.