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.
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.
Authors: Igal Madar; Hayden T Ravert; Yong Du; John Hilton; Lana Volokh; Robert F Dannals; James J Frost; Joshua M Hare Journal: J Nucl Med Date: 2006-08 Impact factor: 10.057
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Authors: S G Nekolla; S Reder; A Saraste; T Higuchi; G Dzewas; A Preissel; M Huisman; T Poethko; T Schuster; M Yu; S Robinson; D Casebier; J Henke; H J Wester; M Schwaiger Journal: Circulation Date: 2009-04-20 Impact factor: 29.690
Authors: Padmaja Yalamanchili; Eric Wexler; Megan Hayes; Ming Yu; Jody Bozek; Mikhail Kagan; Heike S Radeke; Michael Azure; Ajay Purohit; David S Casebier; Simon P Robinson Journal: J Nucl Cardiol Date: 2007-10-22 Impact factor: 5.952
Authors: Hossam M Sherif; Antti Saraste; Eliane Weidl; Axel W Weber; Takahiro Higuchi; Sybille Reder; Thorsten Poethko; Gjermund Henriksen; David Casebier; Simon Robinson; Hans-Jürgen Wester; Stephan G Nekolla; Markus Schwaiger Journal: Circ Cardiovasc Imaging Date: 2009-01-26 Impact factor: 7.792