Universität zu Köln

Stegmayr, Carina ORCID: 0000-0003-4191-8734, Oliveira, Dennis, Niemietz, Nicole, Willuweit, Antje ORCID: 0000-0002-6725-0755, Lohmann, Philipp ORCID: 0000-0002-5360-046X, Galldiks, Norbert ORCID: 0000-0002-2485-1796, Shah, N. Jon ORCID: 0000-0002-8151-6169, Ermert, Johannes ORCID: 0000-0002-2561-7766 and Langen, Karl-Josef ORCID: 0000-0003-1101-5075 (2017). Influence of Bevacizumab on Blood Brain Barrier Permeability and O-(2-F-18-Fluoroethyl)-L-Tyrosine Uptake in Rat Gliomas. J. Nucl. Med., 58 (5). S. 700 - 706. RESTON: SOC NUCLEAR MEDICINE INC. ISSN 1535-5667

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Abstract

Restoration of the blood-brain barrier (BBB) after antiangiogenic therapy of gliomas with bevacizumab may result in a decrease in contrast enhancement on MRI despite tumor progression. This so-called pseudoresponse is difficult to differentiate from a true tumor response with conventional MRI. Initial patient studies have indicated that PET using O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) may be helpful for solving this diagnostic problem. This study was performed to investigate the effects of bevacizumab on BBB permeability and F-18-FET uptake in a human xenograft model. Methods: Human U87 glioblastoma cells were implanted into the striatum of immunodeficient RNU rats. F-18-FET PET scans and ex vivo autoradiography were performed in animals receiving a single high dose of bevacizumab (45 mg/kg 2 d before PET; n = 9) or in animals receiving 2 lower doses (10 mg/kg 9 and 2 d before PET; n = 10) to evaluate short-term and long-term effects on the BBB, respectively, and in control animals without bevacizumab treatment (n = 8). Time-activity curves, slope, and tumor-to-brain ratios of F-18-FET uptake (18-61 min after injection) were evaluated using a volume-of-interest analysis. After PET scanning, Evans blue dye (EBD) was injected into animals, and cryosections of the brains were evaluated by autoradiography, by histology, and for EBD fluorescence to assess BBB permeability. Results: Compared with the control, short-term bevacizumab therapy resulted in a trend toward BBB restoration (P = 0.055) and long-term therapy resulted in a significant decrease (P = 0.004) in BBB permeability, as assessed by EBD fluorescence. In contrast, no significant differences in tumor-to brain ratios or slope of F-18-FET uptake were observed in PET and autoradiography (P > 0.05). Conclusion: F-18-FET uptake in glioblastomas seems to be largely independent of BBB permeability and reflects the viability of tumor tissue during antiangiogenic therapy more reliably than contrast-enhanced MRI.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stegmayr, Carina UNSPECIFIED orcid.org/0000-0003-4191-8734 UNSPECIFIED Oliveira, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED Niemietz, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Willuweit, Antje UNSPECIFIED orcid.org/0000-0002-6725-0755 UNSPECIFIED Lohmann, Philipp UNSPECIFIED orcid.org/0000-0002-5360-046X UNSPECIFIED Galldiks, Norbert UNSPECIFIED orcid.org/0000-0002-2485-1796 UNSPECIFIED Shah, N. Jon UNSPECIFIED orcid.org/0000-0002-8151-6169 UNSPECIFIED Ermert, Johannes UNSPECIFIED orcid.org/0000-0002-2561-7766 UNSPECIFIED Langen, Karl-Josef UNSPECIFIED orcid.org/0000-0003-1101-5075 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-232662
DOI:	10.2967/jnumed.116.187047
Journal or Publication Title:	J. Nucl. Med.
Volume:	58
Number:	5
Page Range:	S. 700 - 706
Date:	2017
Publisher:	SOC NUCLEAR MEDICINE INC
Place of Publication:	RESTON
ISSN:	1535-5667
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VALUABLE DIAGNOSTIC-TOOL; AMINO-ACID PET; RESPONSE ASSESSMENT; UPTAKE KINETICS; F-18-FET PET; EMISSION-TOMOGRAPHY; PROGNOSTIC VALUE; SINGLE-AGENT; FET PET; NEUROONCOLOGY Multiple languages Radiology, Nuclear Medicine & Medical Imaging Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23266