13031
2013
eng
e56317
3
8
article
1
2016-03-18
--
--
Imaging of Intratumoral Inflammation during Oncolytic Virotherapy of Tumors by \(^{19}\)F-Magnetic Resonance Imaging (MRI)
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 \(^1H\)/\(^{19}\)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.
PLoS ONE
10.1371/journal.pone.0056317
urn:nbn:de:bvb:20-opus-130311
PLoS ONE 8(2): e56317. doi:10.1371/journal.pone.0056317
Stephanie Weibel
Thomas Christian Basse-Luesebrink
Michael Hess
Elisabeth Hofmann
Carolin Seubert
Johanna Langbein-Laugwitz
Ivaylo Gentschev
Volker Jörg Friedrich Sturm
Yuxiang Ye
Thomas Kampf
Peter Michael Jakob
Aladar A. Szalay
eng
uncontrolled
inflammation
eng
uncontrolled
fluorescence microscopy
eng
uncontrolled
oncolytic viruses
eng
uncontrolled
fluorescence imaging
eng
uncontrolled
macrophages
eng
uncontrolled
magnetic resonance imaging
eng
uncontrolled
histology
eng
uncontrolled
in vivo imaging
Biochemie
open_access
Physikalisches Institut
Institut für Molekulare Infektionsbiologie
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13031/104_Weibel_Imaging_of_Intratumoral.pdf
11967
2014
eng
e98533
6
9
article
1
2015-10-02
--
--
Characterization of Metastasis Formation and Virotherapy in the Human C33A Cervical Cancer Model
More than 90% of cancer mortalities are due to cancer that has metastasized. Therefore, it is crucial to intensify research on metastasis formation and therapy. Here, we describe for the first time the metastasizing ability of the human cervical cancer cell line C33A in athymic nude mice after subcutaneous implantation of tumor cells. In this model, we demonstrated a steady progression of lumbar and renal lymph node metastases during tumor development. Besides predominantly occurring lymphatic metastases, we visualized the formation of hematogenous metastases utilizing red fluorescent protein (RFP) expressing C33A-RFP cells. RFP positive cancer cells were found migrating in blood vessels and forming micrometastases in lungs of tumor-bearing mice. Next, we set out to analyze the influence of oncolytic virotherapy in the C33A-RFP model and demonstrated an efficient virus-mediated reduction of tumor size and metastatic burden. These results suggest the C33A-RFP cervical cancer model as a new platform to analyze cancer metastases as well as to test novel treatment options to combat metastases.
PLoS ONE
10.1371/journal.pone.0098533
1932-6203
24887184
urn:nbn:de:bvb:20-opus-119674
PLoS ONE 9(6): e98533. doi:10.1371/journal.pone.0098533
Ulrike Donat
Juliane Rother
Simon Schäfer
Michael Hess
Barbara Härtl
Christina Kober
Johanna Langbein-Laugwitz
Jochen Stritzker
Nanhai G. Chen
Richard J. Aguilar
Stephanie Weibel
Alandar A. Szalay
eng
uncontrolled
metastasis
eng
uncontrolled
renal cancer
eng
uncontrolled
oncolytic viruses
eng
uncontrolled
lymph nodes
eng
uncontrolled
kidneys
eng
uncontrolled
lung and intrathoracic tumors
eng
uncontrolled
secondary lung tumors
eng
uncontrolled
cancer treatment
Krankheiten
open_access
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11967/047_Donat_PLOS_ONE.pdf