The feasibility of [18F]EF5-PET/CT to image hypoxia in ovarian tumors: a clinical study

Laasik, Maren; Hynninen, Johanna; Forsbäck, Sarita; Noponen, Tommi; Seppänen, Marko; Hietanen, Sakari

doi:10.1186/s13550-020-00689-z

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…Hypoxia is a common condition reported in several cancers, with 50% to 60% of solid tumors exhibiting hypoxic regions. 25 This metabolic alteration acts as a driver of cancer progression. Hypoxia can enhance the expression of GLUT5, as HIF-1α is tightly associated with GLUT5 in BRCA.…”

Section: Discussionmentioning

confidence: 99%

Construction and Verification of a Hypoxia-Related 4-lncRNA Model for Prediction of Breast Cancer

Zhao¹,

Liu²,

Zhao³

et al. 2021

IJGM

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Introduction Breast cancer is the most common form of cancer worldwide and a serious threat to women. Hypoxia is thought to be associated with poor prognosis of patients with cancer. Long non-coding RNAs are differentially expressed during tumorigenesis and can serve as unambiguous molecular biomarkers for the prognosis of breast cancer. Methods Here, we accessed the data from The Cancer Genome Atlas for model construction and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to identify biological functions. Four prognostic hypoxia-related lncRNAs identified by univariate, LASSO, and multivariate Cox regression analyses were used to develop a prognostic risk-related signature. Kaplan–Meier and receiver operating characteristic curve analyses were performed, and independent prognostic factor analysis and correlation analysis with clinical characteristics were utilized to evaluate the specificity and sensitivity of the signature. Survival analysis and receiver operating characteristic curve analyses of the validation cohort were operated to corroborate the robustness of the model. Results Our results demonstrate the development of a reliable prognostic gene signature comprising four long non-coding RNAs (AL031316.1, AC004585.1, LINC01235, and ACTA2-AS1). The signature displayed irreplaceable prognostic power for overall survival in patients with breast cancer in both the training and validation cohorts. Furthermore, immune cell infiltration analysis revealed that B cells, CD4 T cells, CD8 T cells, neutrophils, and dendritic cells were significantly different between the high-risk and low-risk groups. The high-risk and low-risk groups could be precisely distinguished using the risk signature to predict patient outcomes. Discussion In summary, our study proves that hypoxia-related long non-coding RNAs serve as accurate indicators of poor prognosis and short overall survival, and are likely to act as potential targets for future cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Construction and Verification of a Hypoxia-Related 4-lncRNA Model for Prediction of Breast Cancer

Zhao¹,

Liu²,

Zhao³

et al. 2021

IJGM

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“…A likely explanation for the difficulty in using 18 F-EF5 PET to quantify hypoxia in clinical prostate tumours is the diffuse nature of prostate cancer within the prostate gland. Rather than a single tumour mass as is typical of solid tumour types that exhibit high 18 F-EF5 T/M ratios that indicate tumour hypoxia [17][18][19][20][21], prostate tumours tend to be multi-focal, with cancerous cells interspersed throughout the prostate. Since hypoxic tumour cells make up only a fraction of tumour cells in a given lesion, quantifying 18 F-EF5 uptake in a fraction of prostate tumour cells may be limited by the detection sensitivity of PET.…”

Section: Discussionmentioning

confidence: 99%

“…EF5 has been extensively used in pre-clinical studies across many tumour types to label and quantify hypoxic tumour cells and has shown promising results in clinical settings with head and neck cancer, including correlation with patient outcome [17]. PET measurement of 18 F-EF5 uptake has been used to quantify tumour hypoxia in lung cancer [18], head and neck cancer [17,19,20], and ovarian cancer [21]. Yapp et al previously found 18 F-EF5 PET to effectively detect hypoxia in the Shionogi model of prostate cancer, in both the androgen-dependent and independent phases of the model [22,23], but 18 F-EF5 PET has yet to be tested for detecting hypoxia in clinical prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of ¹⁸F-EF5 for detection of hypoxia in localized adenocarcinoma of the prostate

et al. 2021

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Background: A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18 F-labeled hypoxia reporters. Although the 2-nitroimidazole 18 F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18 F-EF5 to detect hypoxia in clinical prostate tumours. Material and methods: Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18 F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. Results: We found low tumour-to-muscle ratios of 18 F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Conclusion: Our data do not support the use of 18 F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.

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“…[ 18 F]-EF5 was studied in NSCLC and the tracer uptake was correlated to tumor hypoxia ( 105 , 106 ). This tracer was studied in ovarian cancers but this indication appeared to be limited due to the relatively weak uptake in tumors and the biliary excretion may impose limitations on assessing hypoxic tumors located near to the intestine ( 107 ). The injected dose is usually 4 MBq/kg or a fixed activity of 300 MBq.…”

Section: Medical Imagingmentioning

confidence: 99%

Advances in PET and MRI imaging of tumor hypoxia

et al. 2023

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Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging allows to approach these variations, but the tracers used have their own limitations. PET imaging has the disadvantage of low resolution and must take into account molecular biodistribution, but has the advantage of high targeting accuracy. The relationship between the signal in MRI imaging and oxygen is complex but hopefully it would lead to the detection of truly oxygen-depleted tissue. Different ways of imaging hypoxia are discussed in this review, with nuclear medicine tracers such as [18F]-FMISO, [18F]-FAZA, or [64Cu]-ATSM but also with MRI techniques such as perfusion imaging, diffusion MRI or oxygen-enhanced MRI. Hypoxia is a pejorative factor regarding aggressiveness, tumor dissemination and resistance to treatments. Therefore, having accurate tools is particularly important.

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The feasibility of [18F]EF5-PET/CT to image hypoxia in ovarian tumors: a clinical study

Cited by 5 publications

References 26 publications

Construction and Verification of a Hypoxia-Related 4-lncRNA Model for Prediction of Breast Cancer

Construction and Verification of a Hypoxia-Related 4-lncRNA Model for Prediction of Breast Cancer

Evaluation of ¹⁸F-EF5 for detection of hypoxia in localized adenocarcinoma of the prostate

Advances in PET and MRI imaging of tumor hypoxia

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The feasibility of [18F]EF5-PET/CT to image hypoxia in ovarian tumors: a clinical study

Cited by 5 publications

References 26 publications

Construction and Verification of a Hypoxia-Related 4-lncRNA Model for Prediction of Breast Cancer

Construction and Verification of a Hypoxia-Related 4-lncRNA Model for Prediction of Breast Cancer

Evaluation of 18F-EF5 for detection of hypoxia in localized adenocarcinoma of the prostate

Advances in PET and MRI imaging of tumor hypoxia

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Evaluation of ¹⁸F-EF5 for detection of hypoxia in localized adenocarcinoma of the prostate