@article{WeibelBasseLuesebrinkHessetal.2013,
  author    = {Weibel, Stephanie and Basse-Luesebrink, Thomas Christian and Hess, Michael and Hofmann, Elisabeth and Seubert, Carolin and Langbein-Laugwitz, Johanna and Gentschev, Ivaylo and Sturm, Volker J{\"o}rg Friedrich and Ye, Yuxiang and Kampf, Thomas and Jakob, Peter Michael and Szalay, Aladar A.},
  title     = {Imaging of Intratumoral Inflammation during Oncolytic Virotherapy of Tumors by \(^{19}\)F-Magnetic Resonance Imaging (MRI)},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0056317},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130311},
  pages     = {e56317},
  year      = {2013},
  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 \(^1H\)/\(^{19}\)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.},
  language  = {en}
}
@article{HillStritzkerScadengetal.2011,
  author    = {Hill, Philip J. and Stritzker, Jochen and Scadeng, Miriam and Geissinger, Ulrike and Haddad, Daniel and Basse-L{\"u}sebrink, Thomas C. and Gbureck, Uwe and Jakob, Peter and Szalay, Aladar A.},
  title     = {Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing \(Escherichia\) \(coli\)},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0025409},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140920},
  pages     = {e25409},
  year      = {2011},
  abstract  = {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.},
  language  = {en}
}