From the Departments of Interventional Radiology (M.P.M., T.A.F., L.T., Y.Q., N.M.M., K.D., A.M., S.G., A.L.T.), Veterinary Medicine and Surgery (M.G., J.M., M.M.), and Imaging Physics (D.T.F., K.L.M.), the University of Texas M.D. Anderson Cancer Center, PO Box 301402, Unit 1471; Houston, TX 77230-1402; and Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston, Tex (J.G., J.E.E.).
Radiology. 2018 Jan;286(1):149-157. doi: 10.1148/radiol.2017161721. Epub 2017 Aug 21.
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 mm ± 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 -38.5% ± 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 SPIO-DOX and IRE demonstrate enhanced antitumor effect as compared with individual treatments alone. RSNA, 2017 Online supplemental material is available for this article.
评估不可逆电穿孔（IRE）后骨髓细胞中是否形成纳米孔，并评估 IRE 的抗肿瘤作用，IRE 单独或与载多柔比星（DOX）超顺磁性氧化铁（SPIO）纳米颗粒（SPIO-DOX）联合应用于 VX2 兔胫骨肿瘤模型中的作用。
所有实验均经机构动物护理和使用委员会批准。一只猪的 5 个猪椎体接受了介入治疗（IRE 电极放置而不消融 [n = 1]、仅注射纳米颗粒 [n = 1] 和注射纳米颗粒后进行 IRE [n = 3]）。处死动物，采集椎体，用扫描电子显微镜进行评估。12 只兔 VX2 胫骨肿瘤接受治疗，IRE 治疗 3 只，SPIO-DOX 治疗 3 只，SPIO-DOX 联合 IRE 治疗 6 只；5 只兔 VX2 胫骨肿瘤未治疗（对照组）。接种后 9 天和治疗后 2 小时和 5 天，进行动态 T2*-加权 4.7-T 磁共振（MR）成像。用 T2*-加权 MR 成像的肿瘤生长比值和组织学检查的坏死百分比来表示抗肿瘤效果。采用混合效应线性模型分析数据。
扫描电子显微镜显示仅在 IRE 后骨髓细胞中有纳米孔（P ，.01）。治疗前（503.1mm±204.6）肿瘤总体积与治疗后无显著差异（P =.7）。SPIO-DOX 在治疗后 5 天内被识别为肿瘤内信号强度降低，与铁的存在有关。对照治疗的平均肿瘤生长比为 103.0%±75.8，SPIO-DOX 为 154.3%±79.7，IRE 为 77%±30.8，SPIO-DOX 和 IRE 联合治疗为-38.5%±24.8（P =.02）。与对照组（P =.02）、SPIO-DOX（P ，.001）和 IRE（P =.03）治疗相比，联合治疗时骨内残余存活肿瘤的百分比明显较低。与 SPIO-DOX 相比，IRE（P =.005）和 SPIO-DOX 联合 IRE（P =.005）治疗时软组织内残余存活肿瘤的百分比明显较低。
IRE 可诱导骨髓细胞形成纳米孔。与单独治疗相比，SPIO-DOX 和 IRE 联合治疗的胫骨 VX2 肿瘤显示出增强的抗肿瘤作用。
RSNA，2017 在线补充材料可为本文提供。
