TY - JOUR
T1 - MRI-monitored intra-tumoral injection of iron-oxide labeled Clostridium novyi-NT anaerobes in pancreatic carcinoma mouse model
AU - Zheng, Linfeng
AU - Zhang, Zhuoli
AU - Khazaie, Khashayarsha
AU - Saha, Saurabh
AU - Lewandowski, Robert J.
AU - Zhang, Guixiang
AU - Larson, Andrew C.
N1 - Publisher Copyright:
© 2014 Zheng et al.
PY - 2014/12/30
Y1 - 2014/12/30
N2 - Objectives: To validate the feasibility of labeling Clostridium novyi-NT (C.novyi-NT) anaerobes with iron-oxide nanoparticles for magnetic resonance imaging (MRI) and demonstrate the potential to use MRI to visualize intra-tumoral delivery of these iron-oxide labeled C.novyi-NT during percutaneous injection procedures. Materials and Methods: All studies were approved by IACUC. C.novyi-NT were labeled with hybrid iron-oxide Texas red nanoparticles. Growth of labeled and control samples were evaluated with optical density. Labeling was confirmed with confocal fluorescence and transmission electron microscopy (TEM). MRI were performed using a 7 Tesla scanner with T2∗-weighted (T2∗W) sequence. Contrast-to-noise ratio (CNR) measurements were performed for phantoms and signal-to-noise ratio (SNR) measurements performed in C57BL/6 mice (n=12) with Panc02 xenografts before and after percutaneous injection of iron-oxide labeled C.novyi-NT. MRI was repeated 3 and 7 days post-injection. Hematoxylin-eosin (HE), Prussian blue and Gram staining of tumor specimens were performed for confirmation of intra-tumoral delivery. Results: Iron-oxide labeling had no influence upon C.novyi-NT growth. The signal intensity (SI) within T2∗W images was significantly decreased for iron-oxide labeled C.novyi-NT phantoms compared to unlabeled controls. Under confocal fluorescence microscopy, the iron-oxide labeled C.novyi-NT exhibited a uniform red fluorescence consistent with observed regions of DAPI staining and overall labeling efficiency was 100% (all DAPI stained C.novyi-NT exhibited red fluorescence). Within TEM images, a large number iron granules were observed within the iron-oxide labeled C.novyi-NT; these were not observed within unlabeled controls. Intraprocedural MRI measurements permitted in vivo visualization of the intra-tumoral distribution of iron-oxide labeled C.novyi-NT following percutaneous injection (depicted as punctate regions of SI reductions within T2∗-weighted images); tumor SNR decreased significantly following intra-tumoral injection of C.novyi-NT (p<0.05); these SNR reductions were maintained at 3 and 7 day follow-up intervals. Prussian blue and Gram staining confirmed presence of the iron-oxide labeled anaerobes. Conclusions: C.novyi-NT can be labeled with iron-oxide nanoparticles for MRI visualization of intra-tumoral deposition following percutaneous injection during bacteriolytic therapy.
AB - Objectives: To validate the feasibility of labeling Clostridium novyi-NT (C.novyi-NT) anaerobes with iron-oxide nanoparticles for magnetic resonance imaging (MRI) and demonstrate the potential to use MRI to visualize intra-tumoral delivery of these iron-oxide labeled C.novyi-NT during percutaneous injection procedures. Materials and Methods: All studies were approved by IACUC. C.novyi-NT were labeled with hybrid iron-oxide Texas red nanoparticles. Growth of labeled and control samples were evaluated with optical density. Labeling was confirmed with confocal fluorescence and transmission electron microscopy (TEM). MRI were performed using a 7 Tesla scanner with T2∗-weighted (T2∗W) sequence. Contrast-to-noise ratio (CNR) measurements were performed for phantoms and signal-to-noise ratio (SNR) measurements performed in C57BL/6 mice (n=12) with Panc02 xenografts before and after percutaneous injection of iron-oxide labeled C.novyi-NT. MRI was repeated 3 and 7 days post-injection. Hematoxylin-eosin (HE), Prussian blue and Gram staining of tumor specimens were performed for confirmation of intra-tumoral delivery. Results: Iron-oxide labeling had no influence upon C.novyi-NT growth. The signal intensity (SI) within T2∗W images was significantly decreased for iron-oxide labeled C.novyi-NT phantoms compared to unlabeled controls. Under confocal fluorescence microscopy, the iron-oxide labeled C.novyi-NT exhibited a uniform red fluorescence consistent with observed regions of DAPI staining and overall labeling efficiency was 100% (all DAPI stained C.novyi-NT exhibited red fluorescence). Within TEM images, a large number iron granules were observed within the iron-oxide labeled C.novyi-NT; these were not observed within unlabeled controls. Intraprocedural MRI measurements permitted in vivo visualization of the intra-tumoral distribution of iron-oxide labeled C.novyi-NT following percutaneous injection (depicted as punctate regions of SI reductions within T2∗-weighted images); tumor SNR decreased significantly following intra-tumoral injection of C.novyi-NT (p<0.05); these SNR reductions were maintained at 3 and 7 day follow-up intervals. Prussian blue and Gram staining confirmed presence of the iron-oxide labeled anaerobes. Conclusions: C.novyi-NT can be labeled with iron-oxide nanoparticles for MRI visualization of intra-tumoral deposition following percutaneous injection during bacteriolytic therapy.
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U2 - 10.1371/journal.pone.0116204
DO - 10.1371/journal.pone.0116204
M3 - Article
C2 - 25549324
AN - SCOPUS:84920155671
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 12
M1 - e116204
ER -