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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-03-2017 | Original Article

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

Authors: Carina Stegmayr, Ulrike Bandelow, Dennis Oliveira, Philipp Lohmann, Antje Willuweit, Christian Filss, Norbert Galldiks, Joachim H. R. Lübke, N. Jon Shah, Johannes Ermert, Karl-Josef Langen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2017

Abstract

Purpose

O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) is an established tracer for the diagnosis of brain tumors with PET. This study investigates the influence of blood-brain barrier (BBB) permeability on ¹⁸F-FET uptake in two rat glioma models and one human xenograft model.

Methods

F98 glioma, 9L gliosarcoma or human U87 glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats. Thereafter, animals were divided into a control group and a group receiving injections of the glucocorticoid dexamethasone (Dex). After 12-13 days of tumor growth animals received injection of Evans blue dye (EBD) to visualize BBB disturbance and underwent ¹⁸F-FET PET followed by autoradiography. Time activity curves, standardized uptake values (SUV) and Tumor-to-brain ratios (TBR) of ¹⁸F-FET uptake [18-61 min post injection (p.i.)] were evaluated using a volume-of-Interest (VOI) analysis. BBB disturbance was quantitatively evaluated by EBD fluorescence. The membrane gaps of blood vessel endothelial tight junctions were measured using electron microscopy to visualize ultrastructural BBB alterations in one untreated and one Dex treated F98 glioma. Data were analyzed by two-way ANOVAs.

Results

In Dex treated animals EBD extravasation was significantly reduced in 9L (P < 0.001) and U87 (P = 0.008) models and showed a trend in F98 models (P = 0.053). In contrast, no significant differences of ¹⁸F-FET uptake were observed between Dex treated animals and control group except a decrease of the TBR in the 9L tumor model in PET (P < 0.01). Ultrastructural evaluation of tumor blood vessel endothelia revealed significant reduction of the cleft diameter between endothelial cells after Dex treatment in F98 model (P = 0.010).

Conclusion

Despite a considerable reduction of BBB permeability in rat gliomas after Dex treatment, no relevant changes of ¹⁸F-FET uptake were noted in this experimental study. Thus, ¹⁸F-FET uptake in gliomas appears to be widely independent of the permeability of the BBB.

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Title: Influence of blood-brain barrier permeability on O-(2-18F-fluoroethyl)-L-tyrosine uptake in rat gliomas
Authors: Carina Stegmayr
Ulrike Bandelow
Dennis Oliveira
Philipp Lohmann
Antje Willuweit
Christian Filss
Norbert Galldiks
Joachim H. R. Lübke
N. Jon Shah
Johannes Ermert
Karl-Josef Langen
Publication date: 01-03-2017
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2017
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-016-3508-0

At a glance: The STEP trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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