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Pharmacologic characterization in vitro and in vivo of iodine 123-labeled derivatives of the β-adrenoceptor antagonist CGP 12177, designed for the imaging of cardiac β-receptors

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Potential new radioligands for the noninvasive imaging of cardiac β-adrenoceptors with single-photon emission computed tomography were investigated.

Methods and Results

Two iodinated derivatives of CGP12177 para (S-CYBL2B) and ortho (CYBL2A) substituted CGP12177 and an iodinated form of nadolol (CYBL1) were synthesized. Their affinity was tested in vitro (left ventricular homogenates). The biodistribution of [123I]S-CYBL2B was evaluated in rabbits. Specific binding was assessed by pretreatment of the animals with 0.1 μmol propranolol. The inhibition constant values (in nanomolars, means±SEM; n=3 to 5) were determined at 1.17±0.42, 28800±9260, 11.1±2.1, 53.0±19.9, and 1790±700 for CGP12177, CYBL2A, S-CYBL2B, nadolol, and CYBL1. Myocardial uptake of [123I]S-CYBL2B was not inhibited by pretreatment of the animals with propranolol, but uptake by lung tissue could be blocked by propranolol (0.63%±0.09% vs 0.33%±0.02% % injected dose/g×kg; p<0.05). In isolated right atria, preincubation with S-CYBL2B induced a parallel rightward shift of the concentration-response curve with isoprenaline.

Conclusions

S-CYBL2B shows high affinity for cardiac β-adrenoceptors, but binding proved nonspecific in vivo, whereas binding in lung tissue was specific. These results suggest that S-CYBL2B is probably not a suitable radioligand for receptor imaging.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Room F2-238, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Eric A. Dubois, G. Aernout Somsen, Jan C. van den Bos, Anton G. M. Janssen, Gerard J. Boer, Harry D. Batink, Eric A. van Royen, Martin Pfaffendorf & Pieter A. van Zwieten

  2. Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Eric A. Dubois, G. Aernout Somsen, Jan C. van den Bos, Anton G. M. Janssen, Gerard J. Boer, Harry D. Batink, Eric A. van Royen, Martin Pfaffendorf & Pieter A. van Zwieten

  3. Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Eric A. Dubois, G. Aernout Somsen, Jan C. van den Bos, Anton G. M. Janssen, Gerard J. Boer, Harry D. Batink, Eric A. van Royen, Martin Pfaffendorf & Pieter A. van Zwieten

  4. Cygne B.V. Eindhoven University of Technology, Eindhoven, The Netherlands

    Eric A. Dubois, G. Aernout Somsen, Jan C. van den Bos, Anton G. M. Janssen, Gerard J. Boer, Harry D. Batink, Eric A. van Royen, Martin Pfaffendorf & Pieter A. van Zwieten

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  1. Eric A. Dubois
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Supported by grant D92015 of the Netherlands Heart Foundation.

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Dubois, E.A., Somsen, G.A., van den Bos, J.C. et al. Pharmacologic characterization in vitro and in vivo of iodine 123-labeled derivatives of the β-adrenoceptor antagonist CGP 12177, designed for the imaging of cardiac β-receptors. J Nucl Cardiol 3, 242–252 (1996). https://doi.org/10.1016/S1071-3581(96)90038-0

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  • DOI: https://doi.org/10.1016/S1071-3581(96)90038-0

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