TY - JOUR
T1 - Development of an electroporation and nanoparticle-based therapeutic platform for bone metastases
AU - Melancon, Marites P.
AU - Figueira, Tomas Appleton
AU - Fuentes, David T.
AU - Tian, Li
AU - Qiao, Yang
AU - Gu, Jianhua
AU - Gagea, Mihai
AU - Ensor, Joe E.
AU - Muñoz, Nina M.
AU - Maldonado, Kiersten L.
AU - Dixon, Katherine
AU - McWatters, Amanda
AU - Mitchell, Jennifer
AU - McArthur, Mark
AU - Gupta, Sanjay
AU - Tam, Alda L.
N1 - Funding Information:
Supported by the John S. Dunn Research Foundation, Society of Interventional Radiology (SIR Research Foundation Pilot Research Grant), University of Texas MD Anderson Cancer Center Core Grant (CA16672 Veterinary Medicine and Surgery), Levit Family Endowment, and Radiological Society of North America (2014 Bayer Healthcare/RSNA Research Seed Grant RSD145).
PY - 2018/1
Y1 - 2018/1
N2 - Purpose: To assess for nanopore formation in bone marrow cells after irreversible electroporation (IRE) and to evaluate the antitumoral effect of IRE, used alone or in combination with doxorubicin (DOX)-loaded superparamagnetic iron oxide (SPIO) nanoparticles (SPIO-DOX), in a VX2 rabbit tibial tumor model. Materials and Methods: All experiments were approved by the institutional animal care and use committee. Five porcine vertebral bodies in one pig underwent intervention (IRE electrode placement without ablation [n = 1], nanoparticle injection only [n = 1], and nanoparticle injection followed by IRE [n = 3]). The animal was euthanized and the vertebrae were harvested and evaluated with scanning electron microscopy. Twelve rabbit VX2 tibial tumors were treated, three with IRE, three with SPIO-DOX, and six with SPIO-DOX plus IRE; five rabbit VX2 tibial tumors were untreated (control group). Dynamic T2∗-weighted 4.7-T magnetic resonance (MR) images were obtained 9 days after inoculation and 2 hours and 5 days after treatment. Antitumor effect was expressed as the tumor growth ratio at T2∗-weighted MR imaging and percentage necrosis at histologic examination. Mixed-effects linear models were used to analyze the data. Results: Scanning electron microscopy demonstrated nanopores in bone marrow cells only after IRE (P < .01). Average volume of total tumor before treatment (503.1 mm3 ± 204.6) was not significantly different from those after treatment (P = .7). SPIO-DOX was identified as a reduction in signal intensity within the tumor on T2∗-weighted images for up to 5 days after treatment and was related to the presence of iron. Average tumor growth ratios were 103.0% ± 75.8 with control treatment, 154.3% ± 79.7 with SPIO-DOX, 77% ± 30.8 with IRE, and 238.5% ± 24.8 with a combination of SPIO-DOX and IRE (P = .02). The percentage residual viable tumor in bone was significantly less for combination therapy compared with control (P = .02), SPIO-DOX (P < .001), and IRE (P = .03) treatment. The percentage residual viable tumor in soft tissue was significantly less with IRE (P = .005) and SPIO-DOX plus IRE (P = .005) than with SPIO-DOX. Conclusion: IRE can induce nanopore formation in bone marrow cells. Tibial VX2 tumors treated with a combination of SPIODOX and IRE demonstrate enhanced antitumor effect as compared with individual treatments alone.
AB - Purpose: To assess for nanopore formation in bone marrow cells after irreversible electroporation (IRE) and to evaluate the antitumoral effect of IRE, used alone or in combination with doxorubicin (DOX)-loaded superparamagnetic iron oxide (SPIO) nanoparticles (SPIO-DOX), in a VX2 rabbit tibial tumor model. Materials and Methods: All experiments were approved by the institutional animal care and use committee. Five porcine vertebral bodies in one pig underwent intervention (IRE electrode placement without ablation [n = 1], nanoparticle injection only [n = 1], and nanoparticle injection followed by IRE [n = 3]). The animal was euthanized and the vertebrae were harvested and evaluated with scanning electron microscopy. Twelve rabbit VX2 tibial tumors were treated, three with IRE, three with SPIO-DOX, and six with SPIO-DOX plus IRE; five rabbit VX2 tibial tumors were untreated (control group). Dynamic T2∗-weighted 4.7-T magnetic resonance (MR) images were obtained 9 days after inoculation and 2 hours and 5 days after treatment. Antitumor effect was expressed as the tumor growth ratio at T2∗-weighted MR imaging and percentage necrosis at histologic examination. Mixed-effects linear models were used to analyze the data. Results: Scanning electron microscopy demonstrated nanopores in bone marrow cells only after IRE (P < .01). Average volume of total tumor before treatment (503.1 mm3 ± 204.6) was not significantly different from those after treatment (P = .7). SPIO-DOX was identified as a reduction in signal intensity within the tumor on T2∗-weighted images for up to 5 days after treatment and was related to the presence of iron. Average tumor growth ratios were 103.0% ± 75.8 with control treatment, 154.3% ± 79.7 with SPIO-DOX, 77% ± 30.8 with IRE, and 238.5% ± 24.8 with a combination of SPIO-DOX and IRE (P = .02). The percentage residual viable tumor in bone was significantly less for combination therapy compared with control (P = .02), SPIO-DOX (P < .001), and IRE (P = .03) treatment. The percentage residual viable tumor in soft tissue was significantly less with IRE (P = .005) and SPIO-DOX plus IRE (P = .005) than with SPIO-DOX. Conclusion: IRE can induce nanopore formation in bone marrow cells. Tibial VX2 tumors treated with a combination of SPIODOX and IRE demonstrate enhanced antitumor effect as compared with individual treatments alone.
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U2 - 10.1148/radiol.2017161721
DO - 10.1148/radiol.2017161721
M3 - Article
C2 - 28825892
AN - SCOPUS:85038885604
SN - 0033-8419
VL - 286
SP - 149
EP - 157
JO - Radiology
JF - Radiology
IS - 1
ER -