Antiangiogenic Effect of Bevacizumab: Application of Arterial Spin-Labeling Perfusion MR Imaging in a Rat Glioblastoma Model

Tie, Yun; Cho, H.R.; Choi, Seung Hong; Kim, H.; Won, Jae Kyung; Park, Sun Won; Kim, J.-h.; Sohn, Chul‐Ho; Han, Moon Hee

doi:10.3174/ajnr.a4800

Cited by 11 publications

(8 citation statements)

References 25 publications

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“…According to previous studies, a C57BL/6J GBM mouse model that was generated with GL261 cells closely mimicked GBM phenotypes and was partially immunogenic, as the GL261 cells expressed high levels of MHC1. For this reason, recently, many researchers have preferred to use this model to perform immunotherapy-based research 40–44 . Unfortunately, the bolus injection of a contrast agent is difficult in mice due to their very small veins.…”

Section: Discussionmentioning

confidence: 99%

Increased Antiangiogenic Effect by Blocking CCL2-dependent Macrophages in a Rodent Glioblastoma Model: Correlation Study with Dynamic Susceptibility Contrast Perfusion MRI

Cho

Kumari

et al. 2019

Sci Rep

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When glioblastoma multiforme (GBM) is treated with anti-vascular endothelial growth factor (VEGF) agents, it commonly exhibits tumor progression due to the development of resistance, which results in a dismal survival rate. GBM tumors contain a large number of monocytes/macrophages, which have been shown to be resistant to the effects of bevacizumab. It has been reported that tumor-associated macrophages (TAMs) promote resistance to bevacizumab treatment. Therefore, it is important to target TAMs in the GBM microenvironment. TAMs, which depend on chemokine ligand 2 (CCL2) for differentiation and survival, induce the expression of proangiogenic factors such as VEGF. Dynamic susceptibility contrast (DSC)-MR imaging is an advanced technique that provides information on tumor blood volume and can potentially predict the response to several treatments, including anti-angiogenic agents such as bevacizumab, in human GBM. In this study, we used a CCL2 inhibitor, mNOX-E36, to suppress the recruitment of TAMs in a CCL2-expressing rat GBM model and investigated the effect of combination therapy with bevacizumab using DSC-MR imaging. We demonstrated that the inhibition of CCL2 blocked macrophage recruitment and angiogenesis, which resulted in decreased tumor volume and blood volume in CCL2-expressing GBM in a rat model. Our results provide direct evidence that CCL2 expression can increase the resistance to bevacizumab, which can be assessed noninvasively with the DSC-MR imaging technique. This study shows that the suppression of CCL2 can play an important role in increasing the efficacy of anti-angiogenic treatment in GBM by inhibiting the recruitment of CCL2-dependent macrophages.

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Section: Discussionmentioning

confidence: 99%

Increased Antiangiogenic Effect by Blocking CCL2-dependent Macrophages in a Rodent Glioblastoma Model: Correlation Study with Dynamic Susceptibility Contrast Perfusion MRI

Cho

Kumari

et al. 2019

Sci Rep

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“…To the best of our knowledge, no clinical ASL studies are currently available on differentiating responders of antiangiogenic treatment from pseudoresponders. However, in a preclinical study ASL‐derived rCBF values decreased corresponding to a histological response after bevacizumab administration in a glioma rat model …”

Section: Pseudoresponsementioning

confidence: 98%

“…However, in a preclinical study ASL-derived rCBF values decreased corresponding to a histological response after bevacizumab administration in a glioma rat model. 53…”

Section: Pseudoresponsementioning

confidence: 99%

Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques

Dijken

Laar

Smits

et al. 2018

Magnetic Resonance Imaging

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Treatment evaluation of patients with glioblastomas is important to aid in clinical decisions. Conventional MRI with contrast is currently the standard method, but unable to differentiate tumor progression from treatment‐related effects. Pseudoprogression appears as new enhancement, and thus mimics tumor progression on conventional MRI. Contrarily, a decrease in enhancement or edema on conventional MRI during antiangiogenic treatment can be due to pseudoresponse and is not necessarily reflective of a favorable outcome. Neovascularization is a hallmark of tumor progression but not for posttherapeutic effects. Perfusion‐weighted MRI provides a plethora of additional parameters that can help to identify this neovascularization. This review shows that perfusion MRI aids to identify tumor progression, pseudoprogression, and pseudoresponse. The review provides an overview of the most applicable perfusion MRI methods and their limitations. Finally, future developments and remaining challenges of perfusion MRI in treatment evaluation in neuro‐oncology are discussed. Level of Evidence: 3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:11–22.

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“…We, thus, performed ASL-MRI, a noninvasive and quantitative technique that measures perfusion by magnetically labeling water as a freely diffusible endogenous tracer (Silva et al., 2000 ), on large established U87MG tumors (approximately 8 mm 3 ). This technique has already been used in other studies, to evaluate early antiangiogenic treatment responses for brain tumors in humans (Fellah et al., 2011 ; Andre et al., 2015 ) and rodents (Rajendran et al., 2014 ; Towner et al., 2015 ; Yun et al., 2016 ; Ziegler et al., 2017 ). Blood flow in the tumor core was weaker than in normal brain tissue, consistent with the results of Sun et al.…”

Section: Discussionmentioning

confidence: 99%

Development and characterization of sorafenib-loaded lipid nanocapsules for the treatment of glioblastoma

et al. 2018

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Anticancer agents that target both tumor cells and angiogenesis are of potential interest for glioblastoma (GB) therapy. One such agent is sorafenib (SFN), a tyrosine kinase inhibitor. However, poor aqueous solubility and undesirable side effects limit its clinical application, including local treatment. We encapsulated SFN in lipid nanocapsules (LNCs) to overcome these drawbacks. LNCs are nanocarriers formulated according to a solvent-free process, using only components that have received regulatory approval. SFN-LNCs had a diameter of 54 ± 1 nm, high encapsulation efficiency (>90%), and a drug payload of 2.11 ± 0.03 mg/g of LNC dispersion. They inhibited in vitro angiogenesis and decreased human U87MG GB cell viability similarly to free SFN. In vivo studies showed that the intratumoral administration of SFN-LNCs or free SFN in nude mice bearing an orthotopic U87MG human GB xenograft decreased the proportion of proliferating cells in the tumor relative to control groups. SFN-LNCs were more effective than free SFN for inducing early tumor vascular normalization, characterized by increases in tumor blood flow and decreases in tumor vessel area. These results highlight the potential of LNCs as delivery systems for SFN. The vascular normalization induced by SFN-LNCs could be used to improve the efficacy of chemotherapy or radiotherapy for treating GB.

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Antiangiogenic Effect of Bevacizumab: Application of Arterial Spin-Labeling Perfusion MR Imaging in a Rat Glioblastoma Model

Cited by 11 publications

References 25 publications

Increased Antiangiogenic Effect by Blocking CCL2-dependent Macrophages in a Rodent Glioblastoma Model: Correlation Study with Dynamic Susceptibility Contrast Perfusion MRI

Increased Antiangiogenic Effect by Blocking CCL2-dependent Macrophages in a Rodent Glioblastoma Model: Correlation Study with Dynamic Susceptibility Contrast Perfusion MRI

Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques

Development and characterization of sorafenib-loaded lipid nanocapsules for the treatment of glioblastoma

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