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Structure–Activity Relationship and Preclinical Evaluation of Carbon-11-Labeled Ammonium Salts as PET–Myocardial Perfusion Imaging Agents

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Abstract

Background

Due to the limited availability of suitable positron emission tomography (PET) tracers, the majority of myocardial perfusion imaging (MPI) scans is performed using SPECT rather than PET.

Aim

The aim of this study is to design and synthesize carbon-11-labeled ammonium salt derivatives and explore their structure–activity relationship (SAR) and their potential as PET–MPI agents.

Methods and Results

Three carbon-11-labeled ammonium salts were developed. SAR of the labeled compounds were explored vis-à-vis the effects of charge density and lipophilicity on the distribution kinetics in mice. These studies pointed at [11C]4 as the lead compound. Comparative microPET/CT scans in healthy rats, using both [11C]4 and [13 N]–NH3, substantiated the potential of [11C]4 ([11C]-DMDPA). A proof of concept for the potential of radiolabeled ammonium salts as MPI agents has been demonstrated in a newly developed swine model of permanent partial coronary artery occlusion.

Conclusions

SAR studies of 11C-labeled ammonium salts suggest that both lipophilicity and charge density affect the performance of these compounds as MPI probes. In a swine model, the labeled lead successfully visualized the defect regions in the myocardium. The data presented call for the development of fluorine-18 analogues, to increase clinical impact.

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Acknowledgments

The authors wish to thank Rami Marciano, Sassi Cohen, Tomer Yamin, Daniel Wajnblum, Orit Jacobson-Weiss, Darya Tsvirkun, and Marina Orevi for their technical help and their useful advice.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Cyclotron/Radiochemistry Unit/Nuclear Medicine Department, Hadassah Hebrew University Hospital, Jerusalem, 91120, Israel

    Ohad Ilovich, Galith Abourbeh, Hana Billauer, Sharon Dotan & Eyal Mishani

  2. Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, Jerusalem, 91120, Israel

    Moshe Bocher & Nanette Freedman

  3. Interventional Cardiology, Hadassah Hebrew University Hospital, Jerusalem, 91120, Israel

    Haim D. Danenberg

Authors
  1. Ohad Ilovich
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  2. Galith Abourbeh
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  3. Moshe Bocher
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  4. Nanette Freedman
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  5. Hana Billauer
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  6. Sharon Dotan
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  7. Haim D. Danenberg
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  8. Eyal Mishani
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Corresponding author

Correspondence to Eyal Mishani.

Additional information

Authors Ohad Ilovich and Galith Abourbeh equally contributed to this article.

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Ilovich, O., Abourbeh, G., Bocher, M. et al. Structure–Activity Relationship and Preclinical Evaluation of Carbon-11-Labeled Ammonium Salts as PET–Myocardial Perfusion Imaging Agents. Mol Imaging Biol 14, 625–636 (2012). https://doi.org/10.1007/s11307-011-0539-6

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  • DOI: https://doi.org/10.1007/s11307-011-0539-6

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