Development of a Three-Dimensional Multi-Modal Perfusion-Thermal Electrode System for Complete Tumor Eradication.
Development of a Three-Dimensional Multi-Modal Perfusion-Thermal Electrode System for Complete Tumor Eradication.
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图像引导热消融技术，如射频消融（RFA），已成为治疗不可切除的原发性和继发性肿瘤的主要工具。然而，由于肿瘤边缘消融不完全，中大型肿瘤热消融后经常发生肿瘤复发。在本研究中，我们的目标是通过开发一种创新的三维、多模态、灌注热电极系统来彻底改变当前的热消融技术，从而解决这一临床问题，该系统有可能同时将治疗药物和rfa药物在肿瘤周围热疗到难以治疗的肿瘤边缘，从而进一步根除热消融过程中的残留肿瘤细胞。背景：肿瘤周围消融后残留的活细胞是肿瘤复发的来源，导致治疗失败。目的：建立一种新型的三维（3D）多模态灌注-热电极系统，彻底根除大中型恶性肿瘤。材料与方法：本研究包括五个步骤：(1)新系统的设计；（ii）新系统的生产；（iii）体外评价其灌注-热功能；（iv）数学建模和计算机模拟，以确定热烧蚀过程中的最佳温度分布；(v)用5只原位肝肿瘤活兔进行体内技术验证。结果：在离体实验中，大体病理和光学成像显示，通过新电极给药的莫特沙芬钆成功地呈球形分布/沉积，从电极核心在80°C到其外围在42°C的温度梯度。数学模拟与实际动物肿瘤模型之间的温度分布具有良好的重复性（Pearson系数≥0.977）。为了在体内验证，在同时产生中央肿瘤致死射频（RF）热（60°C）和肿瘤周围亚致死射频热（<60°C）的过程中，将吲哚青绿（ICG）直接递送到肿瘤周围区域。光学成像和荧光显微镜证实肿瘤周围ICG分布/沉积成功，热休克蛋白70表达增加。结论：这种新的3D灌注热电极系统为同时将治疗剂和射频热疗送到难以治疗的肿瘤周围区域提供了证据，创造了一种新的策略来解决关键限制，即不可切除的大中型和不规则肿瘤热消融后残余和复发肿瘤的高发生率。
Image-guided thermal-ablation techniques, such as radiofrequency ablation (RFA), have become the principal tools for treatment of unresectable primary and secondary tumors. However, tumor recurrences post-thermal ablation of medium to large-sized tumors frequently occur due to incomplete ablation of tumor margins. In the present study, we aim to specifically conquer this clinical problem through revolutionizing current thermal ablation technology by development of an innovative three-dimensional, multi-modal, perfusion-thermal electrode system, with the evidence of potential to simultaneously deliver therapeutics and RFA-medicated peritumoral hyperthermia into the difficult-to-treat tumor margins, to further eradicate the residual tumor cells during the thermal ablation. Background: Residual viable tumor cells after ablation at the tumor periphery serve as the source for tumor recurrence, leading to treatment failure. Purpose: To develop a novel three-dimensional (3D) multi-modal perfusion-thermal electrode system completely eradicating medium-to-large malignancies. Materials and Methods: This study included five steps: (i) design of the new system; (ii) production of the new system; (iii) ex vivo evaluation of its perfusion-thermal functions; (iv) mathematic modeling and computer simulation to confirm the optimal temperature profiles during the thermal ablation process, and; (v) in vivo technical validation using five living rabbits with orthotopic liver tumors. Results: In ex vivo experiments, gross pathology and optical imaging demonstrated the successful spherical distribution/deposition of motexafin gadolinium administered through the new electrode, with a temperature gradient from the electrode core at 80 °C to its periphery at 42 °C. An excellent repeatable correlation of temperature profiles at varying spots, from the center to periphery of the liver tumor, was found between the mathematic simulation and actual animal tumor models (Pearson coefficient ≥0.977). For in vivo validation, indocyanine green (ICG) was directly delivered into the peritumoral zones during simultaneous generation of central tumoral lethal radiofrequency (RF) heat (>60 °C) and peritumoral sublethal RF hyperthermia (<60 °C). Both optical imaging and fluorescent microscopy confirmed successful peritumoral ICG distribution/deposition with increased heat shock protein 70 expression. Conclusion: This new 3D, perfusion-thermal electrode system provided the evidence on the potential to enable simultaneous delivery of therapeutic agents and RF hyperthermia into the difficult-to-treat peritumoral zones, creating a new strategy to address the critical limitation, i.e., the high incidence of residual and recurrent tumor following thermal ablation of unresectable medium-to-large and irregular tumors.
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影响因子：
11.2
作者：
Kan X;Zhou G;Zhang F;Ji H;Zheng H;Chick JFB;Valji K;Zheng C;Yang X
通讯作者：
Yang X
影响因子：
4
作者：
Hwang JE;Kim SH;Jin J;Hong JY;Kim MJ;Jung SH;Shim HJ;Bae WK;Hwang EC;Kim JW;Shin SS;Jeong O;Park YK;Cho SH;Chung IJ
通讯作者：
Chung IJ
影响因子：
5.8
作者：
Izzo, Francesco;Granata, Vincenza;Curley, Steven A.
通讯作者：
Curley, Steven A.
影响因子：
4.7
作者：
Qian K;Chen M;Zhang F;Chick JFB;Ji H;Zheng C;Yang X
通讯作者：
Yang X
影响因子：
4.6
作者：
Antanavičiūtė I;Mildažienė V;Stankevičius E;Herdegen T;Skeberdis VA
通讯作者：
Skeberdis VA