DCE-MRI of patient-derived xenograft models of uterine cervix carcinoma: associations with parameters of the tumor microenvironment

Hauge, Anette; Wegner, Catherine S.; Gaustad, Jon Vidar; Simonsen, Trude G.; Andersen, Lise Mari K.; Rofstad, Einar K.

doi:10.1186/s12967-017-1331-4

Cited by 18 publications

(26 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DCE-MRI has been specifically applied to the detection of hypoxia in various tumors in an attempt to correlate the results with the pO 2 levels in tissue. This goal has been achieved with unequal results in different types of cancers and a direct correlation between Eppendorf probe results (Cooper et al, 2000 ) and pimoinidazole staining (Hauge et al, 2017 ) has been observed in cervical cancer or prostate cancer (Hoskin et al, 2007 ). However, this correlation with pimoinidazole staining has not been fully clarified thus far in other cases, such as at HNSCC (Newbold et al, 2009 ; Donaldson et al, 2011 ) or [ 18 F]-FMISO uptake in glioblastomas (Swanson et al, 2009 ).…”

Section: Preclinical and Clinical Imaging Of Hypoxiamentioning

confidence: 99%

Oxygen Sensing, Hypoxia Tracing and in Vivo Imaging with Functional Metalloprobes for the Early Detection of Non-communicable Diseases

2018

View full text Add to dashboard Cite

Hypoxia has been identified as one of the hallmarks of tumor environments and a prognosis factor in many cancers. The development of ideal chemical probes for imaging and sensing of hypoxia remains elusive. Crucial characteristics would include a measurable response to subtle variations of pO2 in living systems and an ability to accumulate only in the areas of interest (e.g., targeting hypoxia tissues) whilst exhibiting kinetic stabilities in vitro and in vivo. A sensitive probe would comprise platforms for applications in imaging and therapy for non-communicable diseases (NCDs) relying on sensitive detection of pO2. Just a handful of probes for the in vivo imaging of hypoxia [mainly using positron emission tomography (PET)] have reached the clinical research stage. Many chemical compounds, whilst presenting promising in vitro results as oxygen-sensing probes, are facing considerable disadvantages regarding their general application in vivo. The mechanisms of action of many hypoxia tracers have not been entirely rationalized, especially in the case of metallo-probes. An insight into the hypoxia selectivity mechanisms can allow an optimization of current imaging probes candidates and this will be explored hereby. The mechanistic understanding of the modes of action of coordination compounds under oxygen concentration gradients in living cells allows an expansion of the scope of compounds toward in vivo applications which, in turn, would help translate these into clinical applications. We summarize hereby some of the recent research efforts made toward the discovery of new oxygen sensing molecules having a metal-ligand core. We discuss their applications in vitro and/or in vivo, with an appreciation of a plethora of molecular imaging techniques (mainly reliant on nuclear medicine techniques) currently applied in the detection and tracing of hypoxia in the preclinical and clinical setups. The design of imaging/sensing probe for early-stage diagnosis would longer term avoid invasive procedures providing platforms for therapy monitoring in a variety of NCDs and, particularly, in cancers.

show abstract

Section: Preclinical and Clinical Imaging Of Hypoxiamentioning

confidence: 99%

Oxygen Sensing, Hypoxia Tracing and in Vivo Imaging with Functional Metalloprobes for the Early Detection of Non-communicable Diseases

2018

View full text Add to dashboard Cite

show abstract

“…Clinical investigations have revealed that low K trans values reflect poor vascularization and blood supply in LACC [9,27,28]. Preclinical studies of human cervical carcinoma xenografts have shown strong inverse correlations between median K trans and fraction of hypoxic tumor tissue, regardless of whether radiobiological or pimonidazole-based immunohistochemical assays were used to quantify tumor hypoxia [5,[29][30][31]. Therefore, it is reasonable to assume that RV-K trans mirrors the hypoxic subvolume in tumors of the uterine cervix.…”

Section: Discussionmentioning

confidence: 99%

DCE-MRI of locally-advanced carcinoma of the uterine cervix: Tofts analysis versus non-model-based analyses

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may provide biomarkers of the outcome of locally-advanced cervical carcinoma (LACC). There is, however, no agreement on how DCE-MR recordings should be analyzed. Previously, we have analyzed DCE-MRI data of LACC using non-model-based strategies. In the current study, we analyzed DCE-MRI data of LACC using the Tofts pharmacokinetic model, and the biomarkers derived from this analysis were compared with those derived from the non-model-based analyses. Methods: Eighty LACC patients given cisplatin-based chemoradiotherapy with curative intent were included in the study. Treatment outcome was recorded as disease-free survival (DFS) and overall survival (OS). DCE-MRI series were analyzed voxelwise to produce K trans and v e frequency distributions, and ROC analysis was used to identify the parameters of the frequency distributions having the greatest potential as biomarkers. The prognostic power of these parameters was compared with that of the non-model-based parameters LETV (low-enhancing tumor volume) and TVIS (tumor volume with increasing signal). Results: Poor DFS and OS were associated with low values of K trans , whereas there was no association between treatment outcome and v e . The K trans parameters having the greatest prognostic value were p35-K trans (the K trans value at the 35 percentile of a frequency distribution) and RV-K trans (the tumor subvolume with K trans values below 0.13 min − 1 ). Multivariate analysis including clinical parameters and p35-K trans or RV-K trans revealed that RV-K trans was the only independent prognostic factor of DFS and OS. There were significant correlations between RV-K trans and LETV and between RV-K trans and TVIS, and the prognostic power of RV-K trans was similar to that of LETV and TVIS. Conclusions: Biomarkers of the outcome of LACC can be provided by analyzing DCE-MRI series using the Tofts pharmacokinetic model. However, these biomarkers do not appear to have greater prognostic value than biomarkers determined by non-model-based analyses.

show abstract

“…9 When the K trans value is lower, it is more likely to have poor blood flow and/or low vessel permeability within the tumor area, and thus tumor hypoxia and high HIF-1α expression occurs. 21 Similarly, Hauge et al 22 investigated the potential value of DCE-MRI to assess tumor hypoxia on the basis of xenograft models of cervical carcinoma, and found that, compared with V e , K trans had a higher correlation with the hypoxia fraction for cervical carcinoma. FIGURE 2: DCE perfusion MRI and IVIM DWI in early cervical carcinoma that had low HIF-1α expression.…”

Section: Discussionmentioning

confidence: 99%

Intravoxel Incoherent Motion Combined With Dynamic Contrast‐Enhanced Perfusion MRI of Early Cervical Carcinoma: Correlations Between Multimodal Parameters and HIF‐1α Expression

et al. 2019

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Background The identification of hypoxia inducible factor (HIF‐1α) expression is helpful for the quantitative assessment of tumor hypoxia. The application of multimodal imaging techniques may play a part in the assessment of HIF‐1α expression of cervical carcinoma. Purpose To investigate the correlations between multiple imaging parameters and HIF‐1α expression of early cervical carcinoma and to determine whether tumor hypoxia can be predicted using multisequence imaging parameters. Study Type Prospective observational. Population One hundred patients with early cervical carcinoma. Field Strength/Sequences 3.0 T MRI including intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and dynamic contrast‐enhanced (DCE) perfusion MRI sequences. Assessment DCE‐MRI and IVIM DWI were performed for all patients. The imaging parameters included volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular volume fraction (Ve), D, D*, and f. Statistical Tests The comparisons of imaging parameters between two independent groups were performed using the Mann–Whitney U‐test. Multiple linear regression analysis was performed to determine the correlation between multiple imaging parameters and HIF‐1α expression. The diagnostic ability of DCE‐MRI, IVIM DWI, and the combination of two techniques for discriminating high‐expression and low‐expression groups were analyzed. Results The high‐expression group had a lower Ktrans or Kep value than the low‐expression group (P = 0.03; 0.02), while the high‐expression group had a higher Ve value than the low‐expression group (P = 0.03). The high‐expression group had a higher D or f value than the low‐expression group (P = 0.02; 0.02). Ktrans, Kep, D, Ve, and f values were independently correlated with HIF‐1α expression. The sensitivity or accuracy of a combined method was higher than that of DCE‐MRI or IVIM DWI individually (P = 0.03, 0.02; 0.04, 0.03). Data Conclusion The combination of DCE‐MRI and IVIM DWI can improve the diagnostic ability of discriminating different HIF‐1α expression levels for early cervical tumors. Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:918–929.

show abstract

DCE-MRI of patient-derived xenograft models of uterine cervix carcinoma: associations with parameters of the tumor microenvironment

Cited by 18 publications

References 33 publications

Oxygen Sensing, Hypoxia Tracing and in Vivo Imaging with Functional Metalloprobes for the Early Detection of Non-communicable Diseases

Oxygen Sensing, Hypoxia Tracing and in Vivo Imaging with Functional Metalloprobes for the Early Detection of Non-communicable Diseases

DCE-MRI of locally-advanced carcinoma of the uterine cervix: Tofts analysis versus non-model-based analyses

Intravoxel Incoherent Motion Combined With Dynamic Contrast‐Enhanced Perfusion MRI of Early Cervical Carcinoma: Correlations Between Multimodal Parameters and HIF‐1α Expression

Contact Info

Product

Resources

About