18F-fluorothymidine PET imaging in gliomas: an update

Nikaki, Alexandra V.; Angelidis, George; Efthimiadou, Roxani; Tsougos, Ioannis; Valotassiou, Varvara; Fountas, Konstantinos; Prasopoulos, Vasileios; Georgoulias, Panagiotis

doi:10.1007/s12149-017-1183-2

Cited by 38 publications

(23 citation statements)

References 60 publications

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“…[ 18 F]FLT has been extensively used in the field of oncology to characterize tumors and predict the response to personalized therapeutic approaches ( Schelhaas et al, 2017 ). Therefore, the main application of this radiotracer in neurology has been restricted to the diagnosis of glioblastoma ( Nikaki et al, 2017 ; Brahm et al, 2018 ). Nevertheless, few studies have reported the visualization of endogenous neural stem cells in living animals using [ 18 F]FLT after focal cerebral ischemia, that could be used to monitor the effect of drugs aimed at expanding the neural stem cell niche ( Rueger et al, 2010 , 2012 ).…”

Section: Introductionmentioning

confidence: 99%

In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats

Ardaya¹,

Joya²,

Padró³

et al. 2020

Front. Neurosci.

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In vivo positron emission tomography of neuroinflammation has mainly focused on the evaluation of glial cell activation using radiolabeled ligands. However, the non-invasive imaging of neuroinflammatory cell proliferation has been scarcely evaluated so far. In vivo and ex vivo assessment of gliogenesis after transient middle cerebral artery occlusion (MCAO) in rats was carried out using PET imaging with the marker of cell proliferation 3′-Deoxy-3′-[18F] fluorothymidine ([ 18 F]FLT), magnetic resonance imaging (MRI) and fluorescence immunohistochemistry. MRI-T 2 W studies showed the presence of the brain infarction at 24 h after MCAO affecting cerebral cortex and striatum. In vivo PET imaging showed a significant increase in [ 18 F]FLT uptake in the ischemic territory at day 7 followed by a progressive decline from day 14 to day 28 after ischemia onset. In addition, immunohistochemistry studies using Ki67, CD11b, and GFAP to evaluate proliferation of microglia and astrocytes confirmed the PET findings showing the increase of glial proliferation at day 7 after ischemia followed by decrease later on. Hence, these results show that [ 18 F]FLT provides accurate quantitative information on the time course of glial proliferation in experimental stroke. Finally, this novel brain imaging method might guide on the imaging evaluation of the role of gliogenesis after stroke.

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Section: Introductionmentioning

confidence: 99%

In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats

Ardaya¹,

Joya²,

Padró³

et al. 2020

Front. Neurosci.

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“…18 F-FLT transport is mediated mainly by active Na + -dependent carriers through nucleoside transporters (salvage thymidine pathway) but also by passive diffusion. Similarly to what happens with 18 F-FDG, the tracer is subsequently trapped into the cell thanks to the phosphorylation by thymidine kinase-1 (TK-1) into 18 F-FLT monophosphate which is not incorporated into the DNA chains; TK 1 activity is almost absent in non-replicating cells, whereas its activity reaches the maximum in the late G 1 and S phases of the cell cycle in proliferating cells, thus reflecting tumor proliferation [58]. However, with respect to brain tumors, newer evidence suggests that 18 F-FLT uptake could be also associated with non-specific leakage, thus probably representing BBB breakdown and reflecting an increased permeability, whereas the contribution of the metabolic trapping through TK1 activity seems to be less important.…”

Section: F-fltmentioning

confidence: 99%

The Molecular Effects of Ionizing Radiations on Brain Cells: Radiation Necrosis vs. Tumor Recurrence

et al. 2019

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The central nervous system (CNS) is generally resistant to the effects of radiation, but higher doses, such as those related to radiation therapy, can cause both acute and long-term brain damage. The most important results is a decline in cognitive function that follows, in most cases, cerebral radionecrosis. The essence of radio-induced brain damage is multifactorial, being linked to total administered dose, dose per fraction, tumor volume, duration of irradiation and dependent on complex interactions between multiple brain cell types. Cognitive impairment has been described following brain radiotherapy, but the mechanisms leading to this adverse event remain mostly unknown. In the event of a brain tumor, on follow-up radiological imaging often cannot clearly distinguish between recurrence and necrosis, while, especially in patients that underwent radiation therapy (RT) post-surgery, positron emission tomography (PET) functional imaging, is able to differentiate tumors from reactive phenomena. More recently, efforts have been done to combine both morphological and functional data in a single exam and acquisition thanks to the co-registration of PET/MRI. The future of PET imaging to differentiate between radionecrosis and tumor recurrence could be represented by a third-generation PET tracer already used to reveal the spatial extent of brain inflammation. The aim of the following review is to analyze the effect of ionizing radiations on CNS with specific regard to effect of radiotherapy, focusing the attention on the mechanism underling the radionecrosis and the brain damage, and show the role of nuclear medicine techniques to distinguish necrosis from recurrence and to early detect of cognitive decline after treatment.

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“…Whereas the sensitivity of FLT PET for detecting high-grade gliomas can reach 100%, a lower overall sensitivity of 83% has been shown because of major differences in uptake between high- and low-grade tumors [ 72 73 ]. Hence, the sensitivity of all grades is typically lower than with FDG PET [ 74 ] and methionine PET [ 75 ].…”

Section: Flt Petmentioning

confidence: 99%

Current Radiopharmaceuticals for Positron Emission Tomography of Brain Tumors

Jung

Ahn

2018

Brain Tumor Res Treat

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Brain tumors represent a diverse spectrum of histology, biology, prognosis, and treatment options. Although MRI remains the gold standard for morphological tumor characterization, positron emission tomography (PET) can play a critical role in evaluating disease status. This article focuses on the use of PET with radiolabeled glucose and amino acid analogs to aid in the diagnosis of tumors and differentiate between recurrent tumors and radiation necrosis. The most widely used tracer is 18F-fluorodeoxyglucose (FDG). Although the intensity of FDG uptake is clearly associated with tumor grade, the exact role of FDG PET imaging remains debatable. Additionally, high uptake of FDG in normal grey matter limits its use in some low-grade tumors that may not be visualized. Because of their potential to overcome the limitation of FDG PET of brain tumors, 11C-methionine and 18F-3,4-dihydroxyphenylalanine (FDOPA) have been proposed. Low accumulation of amino acid tracers in normal brains allows the detection of low-grade gliomas and facilitates more precise tumor delineation. These amino acid tracers have higher sensitivity and specificity for detecting brain tumors and differentiating recurrent tumors from post-therapeutic changes. FDG and amino acid tracers may be complementary, and both may be required for assessment of an individual patient. Additional tracers for brain tumor imaging are currently under development. Combinations of different tracers might provide more in-depth information about tumor characteristics, and current limitations may thus be overcome in the near future. PET with various tracers including FDG, 11C-methionine, and FDOPA has improved the management of patients with brain tumors. To evaluate the exact value of PET, however, additional prospective large sample studies are needed.

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18F-fluorothymidine PET imaging in gliomas: an update

Cited by 38 publications

References 60 publications

In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats

In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats

The Molecular Effects of Ionizing Radiations on Brain Cells: Radiation Necrosis vs. Tumor Recurrence

Current Radiopharmaceuticals for Positron Emission Tomography of Brain Tumors

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