Sisson J C, Wieland D M, Koeppe R A, Normolle D, Frey K A, Bolgos G, Johnson J, Van Dort M E, Gildersleeve D L
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028.
J Nucl Med. 1991 Jul;32(7):1399-407.
Myocardial beta adrenergic receptors play important roles in physiology and disease, but the receptors have not before been portrayed. The beta antagonist, iodocyanopindolol (ICYP), was used to develop a scintigraphic method for depicting the receptors in the living heart. Labeled with 125I, ICYP bound firmly to beta receptors in the rat heart; the data conformed to a mathematical model. In vivo saturation kinetics indicated binding sites with two affinities. Inhibition of ICYP binding by beta antagonists of different potency and different selectivity for beta-1 and beta-2 receptors produced the expected pharmacologic effects. Inhibition by lipophilic and hydrophilic antagonists gave no evidence that ICYP was appreciably bound to internalized receptors. Fractional binding by tracer quantities of (-) ICYP and (+/-) ICYP demonstrated stereospecificity. Labeled with 123I, ICYP bound to the hearts of intact dogs so that scintigraphic tomographs depicted ventricular myocardium. Small doses of beta antagonists selectively reduced the binding of ICYP to lung enabling better visualization of the heart. Thus, 123I-ICYP appears to portray the beta receptors in the living heart, and the characteristics of binding permit the development of mathematical models and lay the basis for quantifying this receptor binding.
心肌β肾上腺素能受体在生理和疾病过程中发挥着重要作用，但此前尚未被描绘出来。β拮抗剂碘氰吲哚洛尔（ICYP）被用于开发一种用于描绘活体心脏中这些受体的闪烁成像方法。用125I标记后，ICYP能牢固地结合大鼠心脏中的β受体；数据符合一个数学模型。体内饱和动力学表明存在具有两种亲和力的结合位点。不同效力和对β1和β2受体具有不同选择性的β拮抗剂对ICYP结合的抑制产生了预期的药理作用。亲脂性和亲水性拮抗剂的抑制作用未提供证据表明ICYP与内化受体有明显结合。微量（-）ICYP和（+/-）ICYP的分数结合显示出立体特异性。用123I标记后，ICYP能结合完整犬的心脏，从而使闪烁断层扫描能够描绘心室心肌。小剂量的β拮抗剂选择性地减少了ICYP与肺的结合，从而能更好地观察心脏。因此，123I-ICYP似乎能够描绘活体心脏中的β受体，其结合特性有助于开发数学模型，并为量化这种受体结合奠定基础。
