Characterization of beta-adrenoreceptors in vivo with iodine-131 pindolol and gamma scintigraphy.
The aim of this study to was to assess the feasibility of using iodopindolol to delineate myocardial beta-adrenoreceptors in vivo. Preliminary biodistribution studies indicated that binding of 131I-d,I-pindolol in the heart was stereospecific, saturable, and displaceable by I-propranolol but not by phenoxybenzamine. However, considerable nonspecific binding was encountered. Subsequently, the stereoisomer, 131I-I-pindolol, was shown to be a high affinity beta-adrenoreceptor antagonist (Kd approximately 0.37 nM) as assessed by Scatchard analysis, and one exhibiting marked specific uptake in lung and heart in rabbits. In contrast, 131I-d-pindolol exhibited no specific binding in rabbit left ventricular membrane preparations nor specific organ uptake. Gamma camera scintigraphy with both isomers demonstrated that the I-isomer accumulated in lung and heart, and that its accumulation was blocked by I-propranolol. In contrast, d-isomer uptake was nonspecific and diffuse. The results indicate that it should be possible to externally visualize receptors by differentiating specific and nonspecific binding components of a ligand in vivo with the use of radiolabeled stereoisomers.
D000818:Animals; D007457:Iodine Radioisotopes; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D010869:Pindolol