Imaging hypoxia in gliomas

Mendichovszky, Iosif; Jackson, Alan

doi:10.1259/bjr/82292521

Cited by 65 publications

(40 citation statements)

References 165 publications

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“…It is well establish fact that cancer progression is a consequence of an increasing neoplastic cell load, epigenetic phenotypic changes in neoplastic and stromal cells, genotypic changes and clonal selection of neoplastic cells [100]. Evidence is accumulating that hypoxia not only induces proteome changes influencing tumor propagation but also drives malignant progression through transient and persistent genomic changes in neoplastic cells [101][102][103][104][105]. Interestingly, hypoxia-induced proteome changes in tumor and/or stromal cells In recent years personalizing therapeutic approaches with the aim of identifying patient subpopulations that would benefit from specific targeted therapeutics is heavily favored.…”

Section: Proteogenomic Based Biomarkers To Monitor Radiation Therapy mentioning

confidence: 99%

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

2015

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Section: Proteogenomic Based Biomarkers To Monitor Radiation Therapy mentioning

confidence: 99%

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

2015

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“…Visual assessment of hypoxia is thus worthwhile for diagnosis and treatment in patients with glioblastoma. Positron emission tomography (PET) using hypoxic cell tracers offers an attractive method for detecting hypoxic cells as a simple, minimally invasive, repeatable imaging modality not limited to superficial tumor [1]. Hypoxic cells in glioblastoma have been detected using PET with hypoxic cell tracers including [ [6].…”

Section: Introductionmentioning

confidence: 99%

High-Uptake Areas on 18F-FRP170 PET Image Necessarily Include Proliferating Areas in Glioblastoma: A Superimposed Image Study Combining 18F-FRP170 PET with 11C-methionine PET

Beppu¹,

Sasaki²,

Sato³

et al. 2017

AMI

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Areas of uptake on positron emission tomography with 1-(2-[ 18 F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP170 PET), a hypoxic cell radiotracer, can include regions retaining highly proliferative activity despite tissue hypoxia. The aim of this study was to clarify whether FRP170 image can detect densely populated hypoxic areas without proliferating potential in glioblastoma. We performed FRP170 PET scan and L-methyl-11 C-methionine (MET) PET scan in eight patients with non-treated glioblastoma. Standardized uptake values (SUVs) within tumor and apparent normal brain were measured on each FRP170 and MET image for all patients. To visualize actively proliferative areas on MET image we initially extracted pixels showing a ratio of SUV in tumor to SUV in normal brain (T/N) > 1.6. For FRP170 image, we changed the thresholds between minimum SUV and maximum SUV in tumor. Pixels showing SUV above each threshold were extracted and superimposed on previously extracted pixels from MET image. We estimated whether pixels extracted with MET and FRP170 were visually separated on superimposed image for each patient. When no threshold was established, uptake areas on MET image and FRP170 image overlapped widely on superimposed image in all patients. The higher threshold for FRP170 image diminished FRP170-extracted pixels, and shrunk overlapped areas on superimposed image. However, pixels extracted from FRP170 images could not be completely separated from pixels extracted from MET images in all patients, even with threshold raised to almost maximum SUV. The current findings suggest that uptake areas on FRP170 PET scan necessarily include proliferating areas in glioblastoma.

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“…Indeed, recent studies confirmed that A 2B receptors are activated only when adenosine levels are high, such as in hypoxia or ischemia (Fredholm et al, 2001b). Hypoxia is commonly observed in cancer tissues, and A 2B receptor is highly expressed in cancer tissues (Mendichovszky et al, 2011), suggesting that A 2B receptor might be activated in cancer cells. Importantly, a recent study found that an A 2B adenosine receptor antagonist inhibited growth of bladder and breast tumors via activation of T cell immunity in an IFN- and CXCR3-dependent manner (Cekic et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Adenosine A2B receptor antagonist PSB603 suppresses tumor growth and metastasis by inhibiting induction of regulatory T cells

et al. 2014

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-Regulatory T cells (Treg) play a role in suppression of immune response, including antitumor immunity. We have recently reported that treatment of naïve CD4 T cells with adenosine A 2B receptor antagonist PSB603 under Treg-skewing conditions inhibits expression of Foxp3, a marker of differentiation to Treg, without blocking IL-2 production or CD25 expression, which are activation markers, in CD4 T cells. We hypothesized that PSB603 suppresses cancer growth and metastasis by inhibiting induction of Treg, thereby facilitating anti-tumor immunity. In this study, we first examined the effect of PSB603 on tumor growth in B16 melanoma-bearing C57BL/6 mice. Administration of PSB603 significantly suppressed the increase of tumor volume as well as the increase of Treg population in these mice. The populations of CD4 and CD8 T cells were higher and splenic lymphocyte-mediated cytotoxicity towards B16 melanoma was significantly increased in PSB603-treated mice. We confirmed that PSB603 did not reduce the viability of B16 melanoma cells in vitro. Moreover, we also examined the effect of PSB603 on tumor metastasis in pulmonary metastasis model mice intravenously injected with B16 melanoma cells. The metastasis was also suppressed in PSB603-treated mice, in which the population of Treg was significantly lower. Overall, our results suggest that A 2B receptor antagonist PSB603 enhances anti-tumor immunity by inhibiting differentiation to Treg, resulting in a delay of tumor growth and a suppression of metastasis.

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Imaging hypoxia in gliomas

Cited by 65 publications

References 165 publications

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

High-Uptake Areas on <sup>18</sup>F-FRP170 PET Image Necessarily Include Proliferating Areas in Glioblastoma: A Superimposed Image Study Combining <sup>18</sup>F-FRP170 PET with <sup>11</sup>C-methionine PET

Adenosine A<sub>2B</sub> receptor antagonist PSB603 suppresses tumor growth and metastasis by inhibiting induction of regulatory T cells

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Imaging hypoxia in gliomas

Cited by 65 publications

References 165 publications

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

High-Uptake Areas on &lt;sup&gt;18&lt;/sup&gt;F-FRP170 PET Image Necessarily Include Proliferating Areas in Glioblastoma: A Superimposed Image Study Combining &lt;sup&gt;18&lt;/sup&gt;F-FRP170 PET with &lt;sup&gt;11&lt;/sup&gt;C-methionine PET

Adenosine A<sub>2B</sub> receptor antagonist PSB603 suppresses tumor growth and metastasis by inhibiting induction of regulatory T cells

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High-Uptake Areas on <sup>18</sup>F-FRP170 PET Image Necessarily Include Proliferating Areas in Glioblastoma: A Superimposed Image Study Combining <sup>18</sup>F-FRP170 PET with <sup>11</sup>C-methionine PET