Carbon-11 and Fluorine-18 Radiolabeled Pyridopyrazinone Derivatives for Positron Emission Tomography (PET) Imaging of Phosphodiesterase-5 (PDE5)

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• 作者：Rufael ChekolOlivier Gheysens ; Muneer Ahamed ; Jan Cleynhens ; Peter Pokreisz ; Greet Vanhoof ; Stefan Janssens ; Alfons Verbruggen ; Guy Bormans
• 刊名：Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：January 12, 2017
• 年：2017
• 卷：60
• 期：1
• 页码：486-496
• 全文大小：566K
• ISSN：1520-4804

文摘

The cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) plays an important role in various pathologies including pulmonary arterial hypertension and cardiomyopathy. PDE5 represents an important therapeutic and/or prognostic target, but noninvasive assessment of PDE5 expression is lacking. The purpose of this study was to develop and evaluate pyridopyrazinone derivatives labeled with carbon-11 or fluorine-18 as PDE5-specific PET tracers. In biodistribution studies, highest PDE5-specific retention was observed for [¹¹C]-12 and [¹⁸F]-17 in the lungs of wild-type mice and in the myocardium of transgenic mice with cardiomyocyte-specific PDE5 overexpression at 30 min postinjection. In vivo dynamic microPET images in rats revealed that both tracers crossed the blood–brain barrier but brain retention was not PDE5-specific. Both [¹¹C]-12 and [¹⁸F]-17 showed specific binding to PDE5 in myocardium of transgenic mice; however [¹⁸F]-17 showed significantly higher PDE5-specific inhibitable binding than [¹¹C]-12.