Evaluation of a Novel Macromolecular Cascade-Polymer Contrast Medium for Dynamic Contrast-Enhanced MRI Monitoring of Antiangiogenic Bevacizumab Therapy in a Human Melanoma Model

Cyran, Clemens C.; Fu, Yanjun; Rogut, Victor; Chaopathomkul, Bundit; Wendland, Michael F.; Shames, David M.; Brasch, Robert C.

doi:10.1016/j.acra.2013.07.010

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…In one human study, K trans and v p were reported to be significantly decreased in glioblastoma patients 24 h after the administration of bevacizumab ( Port et al , 2010 ), consistent with our results in OS. In preclinical animal studies, permeability in DCE-MRI was reported to significantly decline 24 h after a single dose of bevacizumab in a human melanoma model ( Cyran et al , 2013 ), but results in other studies 3 days after bevacizumab treatment in a breast xenograft model were inconsistent with increased v p ( Moestue et al , 2013 ) but decreased K trans ( Kim et al , 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI

et al. 2015

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Background:The purpose of this study was to assess the impact of bevacizumab alone and in combination with cytotoxic therapy on tumour vasculature in osteosarcoma (OS) using DCE-MRI.Methods:Six DCE-MRI and three 18F-FDG PET examinations were scheduled in 42 subjects with newly diagnosed OS to monitor the response to antiangiogenic therapy alone and in combination with cytotoxic therapy before definitive surgery (week 10). Serial DCE-MRI parameters (Ktrans, vp, and ve) were examined for correlation with FDG-PET (SUVmax) and association with drug exposure, and evaluated with clinical outcome.Results:Ktrans (P=0.041) and vp (P=0.001) significantly dropped from baseline at 24 h after the first dose of bevacizumab alone, but returned to baseline by 72 h. Greater exposure to bevacizumab was correlated with larger decreases in vp at day 5 (P=0.04) and week 10 (P=0.02). A lower Ktrans at week 10 was associated with greater percent necrosis (P=0.024) and longer event-free survival (P=0.034).Conclusions:This is the first study to demonstrate significant changes of the plasma volume fraction and vascular leakage in OS with bevacizumab alone. The combination of demonstrated associations between drug exposure and imaging metrics, and imaging metrics and patient survival during neoadjuvant therapy, provides a compelling rationale for larger studies using DCE-MRI to assess vascular effects of therapy in OS.

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Section: Discussionmentioning

confidence: 99%

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI

et al. 2015

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“…For example, in oncology, perfusion mapping (as a surrogate measure of blood flow) correlates with response to tyrosine-kinase inhibitor therapy in patients with renal tumors [ 200 ], and quantitative kinetic parameters of lesion enhancement at DCE can predict whether triple-negative breast cancer patients will respond to neoadjuvant chemotherapy [ 201 ]. Animal studies have suggested that quantitative tumor vascularity and perfusion parameters can act as surrogate descriptors for the effect of sorafenib therapy on prostate carcinoma within a week [ 172 ] and that, in conjunction with novel contrast agents, the DCE MRI profile is able to indicate early (within 24 h) endothelial permeability changes following bevacizumab therapy in a melanoma model [ 202 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

25 Years of Contrast-Enhanced MRI: Developments, Current Challenges and Future Perspectives

et al. 2016

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In 1988, the first contrast agent specifically designed for magnetic resonance imaging (MRI), gadopentetate dimeglumine (Magnevist®), became available for clinical use. Since then, a plethora of studies have investigated the potential of MRI contrast agents for diagnostic imaging across the body, including the central nervous system, heart and circulation, breast, lungs, the gastrointestinal, genitourinary, musculoskeletal and lymphatic systems, and even the skin. Today, after 25 years of contrast-enhanced (CE-) MRI in clinical practice, the utility of this diagnostic imaging modality has expanded beyond initial expectations to become an essential tool for disease diagnosis and management worldwide. CE-MRI continues to evolve, with new techniques, advanced technologies, and novel contrast agents bringing exciting opportunities for more sensitive, targeted imaging and improved patient management, along with associated clinical challenges. This review aims to provide an overview on the history of MRI and contrast media development, to highlight certain key advances in the clinical development of CE-MRI, to outline current technical trends and clinical challenges, and to suggest some important future perspectives.FundingBayer HealthCare.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0275-4) contains supplementary material, which is available to authorized users.

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“…32 At the same, in contrast with small molecular MR contrast medium (eg, Gd-DTPA), these dendrimer-based nanoparticles are a type of intracellular medium that makes it feasible to track therapeutic agents at the cellular level. 33 In our study, these nanoparticles produced a relatively high signal intensity that washed out slowly when compared with Gd-DTPA (Figure 4).…”

Section: Resultsmentioning

confidence: 92%

Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer

Wang¹,

Li²,

An³

et al. 2015

IJN

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Background Gene therapy is a very promising technology for treatment of pancreatic ductal adenocarcinoma (PDAC). However, its application has been limited by the abundant stromal response in the tumor microenvironment. The aim of this study was to prepare a dendrimer-based gene-free loading vector with high permeability in the tumor stroma and explore an imaging-guided local gene delivery strategy for PDAC to promote the efficiency of targeted gene delivery. Methods The experimental protocol was approved by the animal ethics committee of Zhongshan Hospital, Fudan University. Third-generation dendrigraft poly-L-lysines was selected as the nanocarrier scaffold, which was modified by cell-penetrating peptides and gadolinium (Gd) chelates. DNA plasmids were loaded with these nanocarriers via electrostatic interaction. The cellular uptake and loaded gene expression were examined in MIA PaCa-2 cell lines in vitro. Permeability of the nanoparticles in the tumor stroma and transfected gene distribution in vivo were studied using a magnetic resonance imaging-guided delivery strategy in an orthotopic nude mouse model of PDAC. Results The nanocarriers were synthesized with a dendrigraft poly-L-lysine to polyethylene glycol to DTPA ratio of 1:3.4:8.3 and a mean diameter of 110.9±7.7 nm. The luciferases were strictly expressed in the tumor, and the luminescence intensity in mice treated by Gd-DPT/plasmid luciferase (1.04×10 4 ±9.75×10 2 p/s/cm 2 /sr) was significantly ( P <0.05) higher than in those treated with Gd-DTPA (9.56×10 2 ±6.15×10 p/s/cm 2 /sr) and Gd-DP (5.75×10 3 ± 7.45×10 2 p/s/cm 2 /sr). Permeability of the nanoparticles modified by cell-penetrating peptides was superior to that of the unmodified counterpart, demonstrating the improved capability of nanoparticles for diffusion in tumor stroma on magnetic resonance imaging. Conclusion This study demonstrated that an image-guided gene delivery system with a stroma-permeable gene vector could be a potential clinically translatable gene therapy strategy for PDAC.

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Evaluation of a Novel Macromolecular Cascade-Polymer Contrast Medium for Dynamic Contrast-Enhanced MRI Monitoring of Antiangiogenic Bevacizumab Therapy in a Human Melanoma Model

Cited by 5 publications

References 34 publications

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI

25 Years of Contrast-Enhanced MRI: Developments, Current Challenges and Future Perspectives

Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer

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