TY  - JOUR
A1  - Weibel, Stephanie
A1  - Basse-Luesebrink, Thomas Christian
A1  - Hess, Michael
A1  - Hofmann, Elisabeth
A1  - Seubert, Carolin
A1  - Langbein-Laugwitz, Johanna
A1  - Gentschev, Ivaylo
A1  - Sturm, Volker Jörg Friedrich
A1  - Ye, Yuxiang
A1  - Kampf, Thomas
A1  - Jakob, Peter Michael
A1  - Szalay, Aladar A.
T1  - Imaging of Intratumoral Inflammation during Oncolytic Virotherapy of Tumors by \(^{19}\)F-Magnetic Resonance Imaging (MRI)
JF  - PLoS ONE
N2  - 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.
KW  - inflammation
KW  - fluorescence microscopy
KW  - oncolytic viruses
KW  - fluorescence imaging
KW  - macrophages
KW  - magnetic resonance imaging
KW  - histology
KW  - in vivo imaging
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130311
VL  - 8
IS  - 3
ER  - 
TY  - JOUR
A1  - Hill, Philip J.
A1  - Stritzker, Jochen
A1  - Scadeng, Miriam
A1  - Geissinger, Ulrike
A1  - Haddad, Daniel
A1  - Basse-Lüsebrink, Thomas C.
A1  - Gbureck, Uwe
A1  - Jakob, Peter
A1  - Szalay, Aladar A.
T1  - Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing \(Escherichia\) \(coli\)
JF  - PLoS ONE
N2  - Background: 

Recent studies have shown that human ferritin can be used as a reporter of gene expression for magnetic resonance imaging (MRI). Bacteria also encode three classes of ferritin-type molecules with iron accumulation properties. 

Methods and Findings: 

Here, we investigated whether these bacterial ferritins can also be used as MRI reporter genes and which of the bacterial ferritins is the most suitable reporter. Bacterial ferritins were overexpressed in probiotic E. coli Nissle 1917. Cultures of these bacteria were analyzed and those generating highest MRI contrast were further investigated in tumor bearing mice. Among members of three classes of bacterial ferritin tested, bacterioferritin showed the most promise as a reporter gene. Although all three proteins accumulated similar amounts of iron when overexpressed individually, bacterioferritin showed the highest contrast change. By site-directed mutagenesis we also show that the heme iron, a unique part of the bacterioferritin molecule, is not critical for MRI contrast change. Tumor-specific induction of bacterioferritin-expression in colonized tumors resulted in contrast changes within the bacteria-colonized tumors.

Conclusions: 

Our data suggest that colonization and gene expression by live vectors expressing bacterioferritin can be monitored by MRI due to contrast changes.
KW  - Blood-brain barrier
KW  - Gene-expression
KW  - Salmonella-typhimurium
KW  - Sugar-transport
KW  - Breast-tumors
KW  - MRI reporter
KW  - Iron-uptake
KW  - Proteins
KW  - Therapy
KW  - Mice
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140920
VL  - 6
IS  - 10
ER  -