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01-10-2012 | Research Article

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

Authors: Ohad Ilovich, Galith Abourbeh, Moshe Bocher, Nanette Freedman, Hana Billauer, Sharon Dotan, Haim D. Danenberg, Eyal Mishani

Published in: Molecular Imaging and Biology | Issue 5/2012

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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Title: Structure–Activity Relationship and Preclinical Evaluation of Carbon-11-Labeled Ammonium Salts as PET–Myocardial Perfusion Imaging Agents
Authors: Ohad Ilovich
Galith Abourbeh
Moshe Bocher
Nanette Freedman
Hana Billauer
Sharon Dotan
Haim D. Danenberg
Eyal Mishani
Publication date: 01-10-2012
Publisher: Springer-Verlag
Published in: Molecular Imaging and Biology / Issue 5/2012
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-011-0539-6

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

Abstract

Background

Aim

Methods and Results

Conclusions

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Springer Medicine

Abstract

Background

Aim

Methods and Results

Conclusions

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