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  • [J Med Chem.] Molecular Imaging of Sirtuin1 Expression-Activity in Rat Brain Using Positron-Emission Tomography-Magnetic-Resonance Imaging with [18F]-2-Fluorobenzoylaminohexanoicanilide.

    Karmanos Cancer Institute / Bonomi R*

  • 출처
    J Med Chem.
  • 등재일
    2018 Aug 23
  • 저널이슈번호
    61(16):7116-7130. doi: 10.1021/acs.jmedchem.8b00253. Epub 2018 Aug 13.
  • 내용

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    Abstract
    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. In vivo imaging of SIRT1 expression-activity should facilitate studies that improve the understanding of SIRT1-mediated regulation in the brain and aid in the development and clinical translation of SIRT1-targeted therapies.

     


    Author information

    Bonomi R1, Popov V1, Laws MT1, Gelovani D1, Majhi A1, Shavrin A1, Lu X, Muzik O, Turkman N1, Liu R2, Mangner T, Gelovani JG1.
    1
    Karmanos Cancer Institute , Detroit , Michigan 48202 , United States.
    2
    National Taiwan University , Taipei City 10617 , Taiwan.

  • 편집위원

    a class III histone deacetylase의 발현 및 활성을 PET/MRI로 정량할 수 있는 novel imaiging agent에 대한 reports

    2018-08-28 11:55:49

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