Influence of blood-brain barrier permeability on O-(2-18F-fluoroethyl)-L-tyrosine uptake in rat gliomas

Stegmayr, Carina; Bandelow, Ulrike; Oliveira, Dennis; Lohmann, Philipp; Willuweit, Antje; Filß, Christian; Galldiks, Norbert; Lübke, Joachim H. R.; Shah, N. Jon; Neumaier, Bernd; Langen, Karl‐Josef

doi:10.1007/s00259-016-3508-0

Cited by 26 publications

(18 citation statements)

References 39 publications

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“…We also showed that the bevacizumab‐induced brain invasion along perivascular spaces, other than PLXDC1 upregulation by the tumor cells, required restoration of the endothelial component of BBB, which would work as a scaffold for migration. In support of this finding, bevacizumab is known to restore the BBB function of U87MG brain xenografts and of human GBM as well . To conclude, our work indicates that the brain infiltration induced by bevacizumab is mainly driven by the vascular endothelium.…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma endothelium drives bevacizumab‐induced infiltrative growth via modulation of PLXDC1

Falchetti

D’Alessandris

Pacioni

et al. 2018

Intl Journal of Cancer

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Bevacizumab, a VEGF‐targeting monoclonal antibody, may trigger an infiltrative growth pattern in glioblastoma. We investigated this pattern using both a human specimen and rat models. In the human specimen, a substantial fraction of infiltrating tumor cells were located along perivascular spaces in close relationship with endothelial cells. Brain xenografts of U87MG cells treated with bevacizumab were smaller than controls (p = 0.0055; Student t‐test), however, bands of tumor cells spread through the brain farther than controls (p < 0.001; Student t‐test). Infiltrating tumor Cells exhibited tropism for vascular structures and propensity to form tubules and niches with endothelial cells. Molecularly, bevacizumab triggered an epithelial to mesenchymal transition with over‐expression of the receptor Plexin Domain Containing 1 (PLXDC1). These results were validated using brain xenografts of patient‐derived glioma stem‐like cells. Enforced expression of PLXDC1 in U87MG cells promoted brain infiltration along perivascular spaces. Importantly, PLXDC1 inhibition prevented perivascular infiltration and significantly increased the survival of bevacizumab‐treated rats. Our study indicates that bevacizumab‐induced brain infiltration is driven by vascular endothelium and depends on PLXDC1 activation of tumor cells.

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Section: Discussionmentioning

confidence: 99%

Glioblastoma endothelium drives bevacizumab‐induced infiltrative growth via modulation of PLXDC1

Falchetti

D’Alessandris

Pacioni

et al. 2018

Intl Journal of Cancer

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“…This is an interesting observation because the underlying mechanisms that determine signal intensities are thought to differ substantially. While the contrast enhancement on MRI represents disruption of the blood-brain barrier (BBB), the increased FET uptake depicted by PET is caused by an overexpression of large neutral amino acid transporters (LAT) leading to an increased accumulation of FET in brain tumors which is not influenced by the BBB permeability (Stegmayr et al, 2017a; Stegmayr et al, 2017b). The observation that the same textural parameters in MRI and FET PET have the highest discriminatory power suggest that patterns of altered amino acid transport and BBB disruption in recurrent metastasis and radionecrosis are altered in the same direction and that there is a fundamental relationship between the physiologically completely different parameters.…”

Section: Discussionmentioning

confidence: 99%

Combined FET PET/MRI radiomics differentiates radiation injury from recurrent brain metastasis

Lohmann

Köcher

Ceccon

et al. 2018

NeuroImage: Clinical

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124

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BackgroundThe aim of this study was to investigate the potential of combined textural feature analysis of contrast-enhanced MRI (CE-MRI) and static O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation between local recurrent brain metastasis and radiation injury since CE-MRI often remains inconclusive.MethodsFifty-two patients with new or progressive contrast-enhancing brain lesions on MRI after radiotherapy (predominantly stereotactic radiosurgery) of brain metastases were additionally investigated using FET PET. Based on histology (n = 19) or clinicoradiological follow-up (n = 33), local recurrent brain metastases were diagnosed in 21 patients (40%) and radiation injury in 31 patients (60%). Forty-two textural features were calculated on both unfiltered and filtered CE-MRI and summed FET PET images (20–40 min p.i.), using the software LIFEx. After feature selection, logistic regression models using a maximum of five features to avoid overfitting were calculated for each imaging modality separately and for the combined FET PET/MRI features. The resulting models were validated using cross-validation. Diagnostic accuracies were calculated for each imaging modality separately as well as for the combined model.ResultsFor the differentiation between radiation injury and recurrence of brain metastasis, textural features extracted from CE-MRI had a diagnostic accuracy of 81% (sensitivity, 67%; specificity, 90%). FET PET textural features revealed a slightly higher diagnostic accuracy of 83% (sensitivity, 88%; specificity, 75%). However, the highest diagnostic accuracy was obtained when combining CE-MRI and FET PET features (accuracy, 89%; sensitivity, 85%; specificity, 96%).ConclusionsOur findings suggest that combined FET PET/CE-MRI radiomics using textural feature analysis offers a great potential to contribute significantly to the management of patients with brain metastases.

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“…Contrast-enhancement in MRI, however, indicates areas with a disrupted blood-brain barrier (BBB) that are, on the one hand, not specific for tumour tissue and, on the other hand, may not detect the full extent of the tumour. In contrast, 18 F-FET uptake is independent of the BBB integrity [62] and allows a more specific delineation of tumour extent than contrast-enhanced MRI [30]. Thus, the results cannot be compared directly and often show discrepancies.…”

Section: Discussionmentioning

confidence: 99%

Hybrid MR-PET of brain tumours using amino acid PET and chemical exchange saturation transfer MRI

Silva

Lohmann

Fairney

et al. 2018

Eur J Nucl Med Mol Imaging

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Influence of blood-brain barrier permeability on O-(2-18F-fluoroethyl)-L-tyrosine uptake in rat gliomas

Abstract: Despite a considerable reduction of BBB permeability in rat gliomas after Dex treatment, no relevant changes of F-FET uptake were noted in this experimental study. Thus,F-FET uptake in gliomas appears to be widely independent of the permeability of the BBB.

Cited by 26 publications

References 39 publications

Glioblastoma endothelium drives bevacizumab‐induced infiltrative growth via modulation of PLXDC1

Glioblastoma endothelium drives bevacizumab‐induced infiltrative growth via modulation of PLXDC1

Combined FET PET/MRI radiomics differentiates radiation injury from recurrent brain metastasis

Hybrid MR-PET of brain tumours using amino acid PET and chemical exchange saturation transfer MRI

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