Dataset Information

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

ABSTRACT:

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-[¹⁸F]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-[¹⁸F]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-[¹⁸F]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-[¹⁸F]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-[¹⁸F]BzAHA SUV and distribution volume in 9L tumors was observed after administration of EX-527, but not MC1568.

Conclusions

PET/CT/MRI with 2-[¹⁸F]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.

SUBMITTER: Laws MT

PROVIDER: S-EPMC7034639 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Dataset Information

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

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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