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  - 
TY  - JOUR
A1  - Szalay, Aladar A.
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
T1  - Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing Escherichia coli
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  - Escherichia coli
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75789
ER  - 
TY  - JOUR
A1  - Kirscher, Lorenz
A1  - Deán-Ben, Xosé Luis
A1  - Scadeng, Miriam
A1  - Zaremba, Angelika
A1  - Zhang, Qian
A1  - Kober, Christina
A1  - Fehm, Thomas Felix
A1  - Razansky, Daniel
A1  - Ntziachristos, Vasilis
A1  - Stritzker, Jochen
A1  - Szalay, Aladar A.
T1  - Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent
JF  - Theranostics
N2  - We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.
KW  - reporter gene
KW  - oncolysis
KW  - molecular imaging
KW  - virotherapy
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124987
VL  - 5
IS  - 10
ER  -