Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects

Increased efficacy of radiotherapy (RT) 4-8 h after Cilengitide treatment has been reported. We hypothesized that the effects of Cilengitide on tumor transvascular transfer parameters might underlie, and thus predict, this potentiation. Athymic rats with orthotopic U251 glioma were studied at ~21 da...

Full description

Bibliographic Details
Main Authors:	Nagaraja, Tavarekere N., Aryal, Madhava P., Brown, Stephen L., Bagher-Ebadian, Hassan, Mikkelsen, Tom, Yang, James J., Panda, Swayamprava, Keenan, Kelly A., Cabral, Glauber, Ewing, James R.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871527/

id	pubmed-3871527
recordtype	oai_dc
spelling	pubmed-38715272013-12-27 Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects Nagaraja, Tavarekere N. Aryal, Madhava P. Brown, Stephen L. Bagher-Ebadian, Hassan Mikkelsen, Tom Yang, James J. Panda, Swayamprava Keenan, Kelly A. Cabral, Glauber Ewing, James R. Research Article Increased efficacy of radiotherapy (RT) 4-8 h after Cilengitide treatment has been reported. We hypothesized that the effects of Cilengitide on tumor transvascular transfer parameters might underlie, and thus predict, this potentiation. Athymic rats with orthotopic U251 glioma were studied at ~21 days after implantation using dynamic contrast-enhanced (DCE)-MRI. Vascular parameters, viz: plasma volume fraction (v p), forward volume transfer constant (K trans) and interstitial volume fraction (v e) of a contrast agent, were determined in tumor vasculature once before, and again in cohorts 2, 4, 8, 12 and 24 h after Cilengitide administration (4 mg/kg; N = 31; 6-7 per cohort). Perfusion-fixed brain sections were stained for von Willebrand factor to visualize vascular segments. A comparison of pre- and post-treatment parameters showed that the differences between MR indices before and after Cilengitide treatment pivoted around the 8 h time point, with 2 and 4 h groups showing increases, 12 and 24 h groups showing decreases, and values at the 8 h time point close to the baseline. The vascular parameter differences between group of 2 and 4 h and group of 12 and 24 h were significant for K trans (p = 0.0001 and v e (p = 0,0271). Vascular staining showed little variation with time after Cilengitide. The vascular normalization occurring 8 h after Cilengitide treatment coincided with similar previous reports of increased treatment efficacy when RT followed Cilengitide by 8 h. Pharmacological normalization of vasculature has the potential to increase sensitivity to RT. Evaluating acute temporal responses of tumor vasculature to putative anti-angiogenic drugs may help in optimizing their combination with other treatment modalities. Public Library of Science 2013-12-23 /pmc/articles/PMC3871527/ /pubmed/24376814 http://dx.doi.org/10.1371/journal.pone.0084493 Text en © 2013 Nagaraja et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Nagaraja, Tavarekere N. Aryal, Madhava P. Brown, Stephen L. Bagher-Ebadian, Hassan Mikkelsen, Tom Yang, James J. Panda, Swayamprava Keenan, Kelly A. Cabral, Glauber Ewing, James R.
spellingShingle	Nagaraja, Tavarekere N. Aryal, Madhava P. Brown, Stephen L. Bagher-Ebadian, Hassan Mikkelsen, Tom Yang, James J. Panda, Swayamprava Keenan, Kelly A. Cabral, Glauber Ewing, James R. Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects
author_facet	Nagaraja, Tavarekere N. Aryal, Madhava P. Brown, Stephen L. Bagher-Ebadian, Hassan Mikkelsen, Tom Yang, James J. Panda, Swayamprava Keenan, Kelly A. Cabral, Glauber Ewing, James R.
author_sort	Nagaraja, Tavarekere N.
title	Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects
title_short	Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects
title_full	Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects
title_fullStr	Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects
title_full_unstemmed	Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects
title_sort	cilengitide-induced temporal variations in transvascular transfer parameters of tumor vasculature in a rat glioma model: identifying potential mri biomarkers of acute effects
description	Increased efficacy of radiotherapy (RT) 4-8 h after Cilengitide treatment has been reported. We hypothesized that the effects of Cilengitide on tumor transvascular transfer parameters might underlie, and thus predict, this potentiation. Athymic rats with orthotopic U251 glioma were studied at ~21 days after implantation using dynamic contrast-enhanced (DCE)-MRI. Vascular parameters, viz: plasma volume fraction (v p), forward volume transfer constant (K trans) and interstitial volume fraction (v e) of a contrast agent, were determined in tumor vasculature once before, and again in cohorts 2, 4, 8, 12 and 24 h after Cilengitide administration (4 mg/kg; N = 31; 6-7 per cohort). Perfusion-fixed brain sections were stained for von Willebrand factor to visualize vascular segments. A comparison of pre- and post-treatment parameters showed that the differences between MR indices before and after Cilengitide treatment pivoted around the 8 h time point, with 2 and 4 h groups showing increases, 12 and 24 h groups showing decreases, and values at the 8 h time point close to the baseline. The vascular parameter differences between group of 2 and 4 h and group of 12 and 24 h were significant for K trans (p = 0.0001 and v e (p = 0,0271). Vascular staining showed little variation with time after Cilengitide. The vascular normalization occurring 8 h after Cilengitide treatment coincided with similar previous reports of increased treatment efficacy when RT followed Cilengitide by 8 h. Pharmacological normalization of vasculature has the potential to increase sensitivity to RT. Evaluating acute temporal responses of tumor vasculature to putative anti-angiogenic drugs may help in optimizing their combination with other treatment modalities.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871527/
_version_	1612040977215651840

Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects

Similar Items