Molecular Imaging of Sirtuin1 Expression–Activity in Rat Brain Using Positron-Emission Tomography–Magnetic-Resonance Imaging with [18F]-2-Fluorobenzoylaminohexanoicanilide
| Autor: | Xin Lu, Otto Muzik, Thomas J. Mangner, Aleksandr Shavrin, Vadim V. Popov, Maxwell T. Laws, David Gelovani, Robin E. Bonomi, Anjoy Majhi, Renshyan Liu, Juri G. Gelovani, Nashaat Turkman |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Positron emission tomography–magnetic resonance imaging medicine.medical_specialty biology Sirtuin 1 Chemistry Hippocampus Nucleus accumbens 03 medical and health sciences 030104 developmental biology Endocrinology Hypothalamus In vivo Internal medicine Drug Discovery medicine biology.protein Molecular Medicine Locus coeruleus Blood sampling |
| Zdroj: | Journal of Medicinal Chemistry. 61:7116-7130 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Sirtuin 1 (SIRT1) is a class III histone deacetylase that plays significant roles in the regulation of lifespan, metabolism, memory, and circadian rhythms and in the mechanisms of many diseases. However, methods of monitoring the pharmacodynamics of SIRT1-targeted drugs are limited to blood sampling because of the invasive nature of biopsies. For the noninvasive monitoring of the spatial and temporal dynamics of SIRT1 expression–activity in vivo by PET–CT–MRI, we developed a novel substrate-type radiotracer, [18F]-2-fluorobenzoylaminohexanoicanilide (2-[18F]BzAHA). PET–CT–MRI studies in rats demonstrated increased accumulation of 2-[18F]BzAHA-derived radioactivity in the hypothalamus, hippocampus, nucleus accumbens, and locus coeruleus, consistent with autoradiographic and immunofluorescent (IMF) analyses of brain-tissue sections. Pretreatment with the SIRT1 specific inhibitor, EX-527 (5 mg/kg, ip), resulted in about a 20% reduction of 2-[18F]BzAHA-derived-radioactivity accumulation in these structures. I... |
| Databáze: | OpenAIRE |
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