Latest Advances in Imaging Oxidative Stress in Cancer

Greenwood, Hannah E.; Witney, Timothy H.

doi:10.2967/jnumed.120.256974

Cited by 17 publications

(16 citation statements)

References 39 publications

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“…Oxidative stress is defined as the excessive generation of ROS, RONs, and other free radicals in the body as a result of numerous damaging stimuli, which surpasses the body's scavenging capability and disrupt the equilibrium of oxidants/antioxidants 39 . When it comes to the normal body, oxidative stress may be harmful, but it may play an important role in tumor cells 40 . NRF2 is one of the important pathways for intracellular antioxidant stress and maintenance of redox.…”

Section: Discussionmentioning

confidence: 99%

Cyperotundone combined with adriamycin induces apoptosis in MCF-7 and MCF-7/ADR cancer cells by ROS generation and NRF2/ARE signaling pathway

Shao

Wang

Liu

et al. 2023

Sci Rep

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Breast cancer has become the most prevalent cancer, globally. Adriamycin is a first-line chemotherapeutic agent, however, cancer cells acquire resistance to it, which is one of the most common causes of treatment failure. ROS and NRF2 are essential oxidative stress factors that play a key role in the oxidative stress process and are associated with cancer. Our goal is to create novel therapeutic drugs or chemical sensitizers that will improve chemotherapy sensitivity. The optimal concentration and duration for MCF-7 and MCF-7/ADR cells in ADR and CYT were determined using the CCK-8 assay. We found that ADR + CYT inhibited the activity of MCF-7 and MCF-7/ADR cells in breast cancer, as well as causing apoptosis in MCF-7 and MCF-7/ADR cells and blocking the cell cycle in the G0/G1 phase. ADR + CYT induces apoptosis in MCF-7 and MCF-7/ADR cells through ROS generation and the P62/NRF2/HO-1 signaling pathway. In breast cancer-bearing nude mice, ADR + CYT effectively suppressed tumor development in vivo. Overall, our findings showed that CYT in combination with ADR has potent anti-breast cancer cell activity both in vivo and in vitro, suggesting CYT as the main drug used to improve chemosensitivity.

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Section: Discussionmentioning

confidence: 99%

Cyperotundone combined with adriamycin induces apoptosis in MCF-7 and MCF-7/ADR cancer cells by ROS generation and NRF2/ARE signaling pathway

Shao

Wang

Liu

et al. 2023

Sci Rep

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“…System x C - can mediate this adaptive cellular response to oxidative stress 17 , 28 , 50 . A non-invasive readout of system x C - activity therefore offers an important understanding into tumor behavior, with the potential to provide insight into drug response and resistance 51 . Here, we investigated whether the chirality of system x C - -specific radiotracers can be exploited for improved tumor imaging of system x C - in cell models and living subjects.…”

Section: Discussionmentioning

confidence: 99%

Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system x_C^- in tumors

Greenwood¹,

Edwards²,

Koglin³

et al. 2022

Theranostics

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Amino acid utilization is perturbed in cancer cells, which rewire their metabolism to support cell survival and proliferation. This metabolic reprogramming can be exploited for diagnostic purposes through positron emission tomography imaging of fluorine-18 labeled amino acids. Despite its promise, little is known regarding transporter-recognition of non-natural amino acid stereoisomers or their utility for cancer imaging. We report here the synthesis and in vivo characterization of a radiolabeled amino acid ( R )-4-(3- 18 F-fluoropropyl)-ʟ-glutamate ([ 18 F]FRPG) and compared its tumor imaging properties to the 4 S -isomer, [ 18 F]FSPG. Methods : [ 18 F]FRPG and [ 18 F]FSPG uptake was assessed in H460 lung cancer cells, with efflux measured 30 min after removal of exogenous activity. Specificity of [ 18 F]FRPG for system x C - was further examined following transporter inhibition and blocking studies with system x C - substrates. [ 18 F]FRPG and [ 18 F]FSPG pharmacokinetics was next quantified in mice bearing subcutaneous A549, H460, VCAP and PC3 tumors, with mice bearing A549 tumors imaged by PET/CT. To better-understand differential tumor retention, radiometabolite analysis was performed on tissue and blood samples after imaging. Next, [ 18 F]FRPG and [ 18 F]FSPG retention in lipopolysaccharide-treated lungs were compared to an orthotopic H460 lung cancer model. Finally, the sensitivity of [ 18 F]FRPG to manipulation of the redox environment was examined in cell and in vivo models. Results : [ 18 F]FRPG was specifically transported across the plasma membrane by the cystine/glutamate antiporter system x C - and retained at high levels in multiple tumor models. Conversely, [ 18 F]FRPG was rapidly extracted from the blood and cleared from tissues with low system x C - expression. Due to its favorable imaging properties, tumor-to-blood ratios ≥10 were achieved with [ 18 F]FRPG, which were either equal to or greater than [ 18 F]FSPG. In addition, [ 18 F]FRPG retention in orthotopic lung tumors with high system x C - expression was 2.5-fold higher than inflamed tissue, allowing for clear tumor visualization. In vivo , [ 18 F]FRPG and [ 18 F]FSPG were metabolized to a single species, with [ 18 F]FRPG showing a higher ...

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“…Development of OS imaging techniques has emerged in the field of neurodegenerative diseases due to altered mitochondrial oxidative metabolism ( 39 – 41 ). More recently, imaging with magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) may allow clinically-relevant quantification of OS non-invasively in vivo .…”

Section: Imaging Oxidative Stressmentioning

confidence: 99%

Oxidative stress in multiple sclerosis—Emerging imaging techniques

et al. 2023

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While conventional magnetic resonance imaging (MRI) is central to the evaluation of patients with multiple sclerosis, its role in detecting the pathophysiology underlying neurodegeneration is more limited. One of the common outcome measures for progressive multiple sclerosis trials, atrophy on brain MRI, is non-specific and reflects end-stage changes after considerable neurodegeneration has occurred. Identifying biomarkers that identify processes underlying neurodegeneration before it is irreversible and that reflect relevant neurodegenerative pathophysiology is an area of significant need. Accumulating evidence suggests that oxidative stress plays a major role in the pathogenesis of multiple neurodegenerative diseases, including multiple sclerosis. Imaging markers related to inflammation, myelination, and neuronal integrity have been areas of advancement in recent years but oxidative stress has remained an area of unrealized potential. In this article we will begin by reviewing the role of oxidative stress in the pathogenesis of multiple sclerosis. Chronic inflammation appears to be directly related to the increased production of reactive oxygen species and the effects of subsequent oxidative stress appear to be amplified by aging and accumulating disease. We will then discuss techniques in development used in the assessment of MS as well as other models of neurodegenerative disease in which oxidative stress is implicated. Multiple blood and CSF markers of oxidative stress have been evaluated in subjects with MS, but non-invasive imaging offers major upside in that it provides real-time assessment within the brain.

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Latest Advances in Imaging Oxidative Stress in Cancer

Cited by 17 publications

References 39 publications

Cyperotundone combined with adriamycin induces apoptosis in MCF-7 and MCF-7/ADR cancer cells by ROS generation and NRF2/ARE signaling pathway

Cyperotundone combined with adriamycin induces apoptosis in MCF-7 and MCF-7/ADR cancer cells by ROS generation and NRF2/ARE signaling pathway

Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system x_C^- in tumors

Oxidative stress in multiple sclerosis—Emerging imaging techniques

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Latest Advances in Imaging Oxidative Stress in Cancer

Cited by 17 publications

References 39 publications

Cyperotundone combined with adriamycin induces apoptosis in MCF-7 and MCF-7/ADR cancer cells by ROS generation and NRF2/ARE signaling pathway

Cyperotundone combined with adriamycin induces apoptosis in MCF-7 and MCF-7/ADR cancer cells by ROS generation and NRF2/ARE signaling pathway

Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system xC- in tumors

Oxidative stress in multiple sclerosis—Emerging imaging techniques

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Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system x_C^- in tumors