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Background  Several studies demonstrated that glioblastoma multiforme progression and recurrence is linked to epigenetic regulatory mechanisms. Sirtuin 1 (SIRT1) plays an important role in glioma progression, invasion, and treatment response and is a potential therapeutic target. The aim of this study is to test the feasibility of 2-[ 18 F]BzAHA for quantitative imaging of SIRT1 expression–activity and monitoring pharmacologic inhibition in a rat model of intracerebral glioma.    Methods  Sprague Dawley rats bearing 9L ( N  = 12) intracerebral gliomas were injected with 2-[ 18 F]BzAHA (300–500 µCi/animal i.v.) and dynamic positron-emission tomography (PET) imaging was performed for 60 min. Then, SIRT1 expression in 9L tumors ( N  = 6) was studied by immunofluorescence microscopy (IF). Two days later, rats with 9L gliomas were treated either with SIRT1 specific inhibitor EX-527 (5 mg/kg, i.p.;  N  = 3) or with histone deacetylases class IIa specific inhibitor MC1568 (30 mg/kg, i.p.;  N  = 3) and 30 min later were injected i.v. with 2-[ 18 F]BzAHA. PET-computerized tomography-magnetic resonance (PET/CT/MR) images acquired after EX-527 and MC1568 treatments were co-registered with baseline images.    Results  Standard uptake values (SUVs) of 2-[ 18 F]BzAHA in 9L tumors measured at 20 min post-radiotracer administration were 1.11 ± 0.058 and had a tumor-to-brainstem SUV ratio of 2.73 ± 0.141. IF of 9L gliomas revealed heterogeneous upregulation of SIRT1, especially in hypoxic and peri-necrotic regions. Significant reduction in 2-[ 18 F]BzAHA SUV and distribution volume in 9L tumors was observed after administration of EX-527, but not MC1568.    Conclusions  PET/CT/MRI with 2-[ 18 F]BzAHA can facilitate studies to elucidate the roles of SIRT1 in gliomagenesis and progression, as well as to optimize therapeutic doses of novel SIRT1 inhibitors.

neuro-oncology advances

Noninvasive quantification of SIRT1 expression–activity and pharmacologic inhibition in a rat model of intracerebral glioma using 2-[18F]BzAHA PET/CT/MRI