Dataset Information

Imaging of intratumoral inflammation during oncolytic virotherapy of tumors by 19F-magnetic resonance imaging (MRI).

ABSTRACT:

Background

Oncolytic virotherapy of tumors is an up-coming, promising therapeutic modality of cancer therapy. Unfortunately, non-invasive techniques to evaluate the inflammatory host response to treatment are rare. Here, we evaluate (19)F magnetic resonance imaging (MRI) which enables the non-invasive visualization of inflammatory processes in pathological conditions by the use of perfluorocarbon nanoemulsions (PFC) for monitoring of oncolytic virotherapy.

Methodology/principal findings

The Vaccinia virus strain GLV-1h68 was used as an oncolytic agent for the treatment of different tumor models. Systemic application of PFC emulsions followed by (1)H/(19)F MRI of mock-infected and GLV-1h68-infected tumor-bearing mice revealed a significant accumulation of the (19)F signal in the tumor rim of virus-treated mice. Histological examination of tumors confirmed a similar spatial distribution of the (19)F signal hot spots and CD68(+)-macrophages. Thereby, the CD68(+)-macrophages encapsulate the GFP-positive viral infection foci. In multiple tumor models, we specifically visualized early inflammatory cell recruitment in Vaccinia virus colonized tumors. Furthermore, we documented that the (19)F signal correlated with the extent of viral spreading within tumors.

Conclusions/significance

These results suggest (19)F MRI as a non-invasive methodology to document the tumor-associated host immune response as well as the extent of intratumoral viral replication. Thus, (19)F MRI represents a new platform to non-invasively investigate the role of the host immune response for therapeutic outcome of oncolytic virotherapy and individual patient response.

SUBMITTER: Weibel S

PROVIDER: S-EPMC3575337 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Imaging of intratumoral inflammation during oncolytic virotherapy of tumors by 19F-magnetic resonance imaging (MRI).

Weibel Stephanie S Basse-Luesebrink Thomas Christian TC Hess Michael M Hofmann Elisabeth E Seubert Carolin C Langbein-Laugwitz Johanna J Gentschev Ivaylo I Sturm Volker Jörg Friedrich VJ Ye Yuxiang Y Kampf Thomas T Jakob Peter Michael PM Szalay Aladar A AA

PloS one 20130218 2

<h4>Background</h4>Oncolytic virotherapy of tumors is an up-coming, promising therapeutic modality of cancer therapy. Unfortunately, non-invasive techniques to evaluate the inflammatory host response to treatment are rare. Here, we evaluate (19)F magnetic resonance imaging (MRI) which enables the non-invasive visualization of inflammatory processes in pathological conditions by the use of perfluorocarbon nanoemulsions (PFC) for monitoring of oncolytic virotherapy.<h4>Methodology/principal findin ...[more]

PMID: 23441176

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Project description:UnlabelledBackgroundNon-invasive imaging of inflammation to measure the progression of autoimmune diseases, such as rheumatoid arthritis (RA), and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon (PFC) contrast agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by 19F MRI. With no 19F background in the host, detection is highly-specific and can act as a proxy biomarker of the degree of inflammation present.MethodsCollagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of the PFC contrast agent to reveal the accumulation of inflammation over time using 19F MRI. Disease progression in the rat hind limbs was monitored by caliper measurements and 19F MRI on days 15, 22 and 29, including the height of clinically symptomatic disease. Naïve rats served as controls. The capacity of the PFC contrast agent and 19F MRI to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28.ResultsQuantification of 19F signal measured by MRI in affected limbs was linearly correlated with disease severity. In animals with progressive disease, increases in 19F signal reflected the ongoing recruitment of inflammatory cells to the site, while no increase in 19F signal was observed in animals receiving treatment which resulted in clinical resolution of disease.ConclusionThese results indicate that 19F MRI may be used to quantitatively and qualitatively evaluate longitudinal responses to a therapeutic regimen, while additionally revealing the recruitment of monocytic cells involved in the inflammatory process to the anatomical site. This study may support the use of 19F MRI to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory component.

Project description:BackgroundMagnetic resonance imaging (MRI) is a promising tool for monitoring stem cell-based therapy. Conventionally, cells loaded with ironoxide nanoparticles appear hypointense on MR images. However, the contrast generated by ironoxide labeled cells is neither specific due to ambiguous background nor quantitative. A strategy to overcome these drawbacks is (19)F MRI of cells labeled with perfluorocarbons. We show here for the first time that human neural stem cells (NSCs), a promising candidate for clinical translation of stem cell-based therapy of the brain, can be labeled with (19)F as well as detected and quantified in vitro and after brain implantation.Methodology/principal findingsHuman NSCs were labeled with perfluoropolyether (PFPE). Labeling efficacy was assessed with (19)F MR spectroscopy, influence of the label on cell phenotypes studied by immunocytochemistry. For in vitro MRI, NSCs were suspended in gelatin at varying densities. For in vivo experiments, labeled NSCs were implanted into the striatum of mice. A decrease of cell viability was observed directly after incubation with PFPE, which re-normalized after 7 days in culture of the replated cells. No label-related changes in the numbers of Ki67, nestin, GFAP, or βIII-tubulin+ cells were detected, both in vitro and on histological sections. We found that 1,000 NSCs were needed to accumulate in one image voxel to generate significant signal-to-noise ratio in vitro. A detection limit of ∼10,000 cells was found in vivo. The location and density of human cells (hunu+) on histological sections correlated well with observations in the (19)F MR images.Conclusion/significanceOur results show that NSCs can be efficiently labeled with (19)F with little effects on viability or proliferation and differentiation capacity. We show for the first time that (19)F MRI can be utilized for tracking human NSCs in brain implantation studies, which ultimately aim for restoring loss of function after acute and neurodegenerative disorders.

Dataset Information

Imaging of intratumoral inflammation during oncolytic virotherapy of tumors by 19F-magnetic resonance imaging (MRI).

Background

Methodology/principal findings

Conclusions/significance

Publications

Imaging of intratumoral inflammation during oncolytic virotherapy of tumors by 19F-magnetic resonance imaging (MRI).

Similar Datasets

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