Development of intravascular targeting hyperthermia using dextran magnetite complex

这是发展“血管内靶向热疗”的基础研究，在这种热疗中，深层肿瘤使用血管内给药的磁性材料和外部施加的交流磁场来加热。作为发热材料，我们使用了葡聚糖磁铁矿络合物(DM)，这是一种‘磁性液体’。由于不同的生热机制，DM在交流磁场中的产热比以前报道的多磁区铁氧体粒子要高得多。我们设计了两种含DM的栓塞剂，DM/碘化油乳剂和DM/可降解淀粉微球(DM/DSM)悬浮液。体外实验表明，这些制剂中DM的生热能力并未降低。将这些材料注入日本大白兔的肾动脉，可实现选择性加热(10ﾟC/10min以上)。暴露在约1…的100 kHz交流磁场中后，栓塞的肾脏栓塞组肾组织铁含量平均为4.9(±0.54)mg/g组织。对一只兔肝脏移植的VX2肿瘤进行了类似的实验，证明了该肿瘤有足够的加热。在目前含有栓塞剂的DM成分中，DM在动脉内给药后6小时内逃逸到体循环，并被网状内皮系统(RES)捕获。此外，一项使用C3H小鼠模型的实验显示，DM在代谢时产热能力降低13EA01：这是开发一种“血管内靶向热疗”的基础研究，在这种热疗中，深层肿瘤使用血管内给药的磁性材料和外部交流磁场进行加热。作为发热材料，我们使用了葡聚糖磁铁矿络合物(DM)，这是一种‘磁性液体’。由于不同的生热机制，DM在交流磁场中的产热比以前报道的多磁区铁氧体粒子要高得多。我们设计了两种含DM的栓塞剂，DM/碘化油乳剂和DM/可降解淀粉微球(DM/DSM)悬浮液。体外实验表明，这些制剂中DM的生热能力并未降低。将这些材料注入日本大白兔的肾动脉，可实现选择性加热(10ﾟC/10min以上)。在约15000 A/m的100 kHz交流磁场作用下，栓塞肾脏的平均铁含量为4.9mgFe/g组织。对一只兔肝脏移植的VX2肿瘤进行了类似的实验，证明了该肿瘤有足够的加热。在目前含有栓塞剂的DM成分中，DM在动脉内给药后6小时内逃逸到体循环，并被网状内皮系统(RES)捕获。此外，更少的实验

This is a fundamental study to develop an "intravascular targeting hyperthermia" , in which a deep seated tumor is heated using an intravascularly administered magnetic material together with an externally applied AC magnetic field. As a heat generating material, we employed dextran magnetite complex (DM) , which is a kind of 'magnetic fluid'. The heat production of DM in an AC magnetic field is much higher than previously reported multidomain ferrite particles due to a different mechanism of heat generation. We designed two DM-containing embolic materials, a DM/Lipiodol(]SY.encircledR.[) emulsion and a DM/degradable starch microsphere (DM/DSM) suspension. In vitro experiments showed that the heat generating capacity of DM was not reduced in these preparations. When these materials were injected into the renal arteries of Japanese white rabbits, they achieved selective heating (over 10ﾟC/10min.) of the embolized kidney following exposure to a 100kHz AC magnetic field of approximately 1 … More 5000 A/m. The average iron concentration in the embolized kidney was 4.9 (]SY.+-.[) 2.4mg Fe/g tissue. A similar experiment with a VX2 tumor transplanted in the liver of a rabbit demonstrated sufficient heating of the tumor. With current composition of DM containing embolic material, DM escapes into systemic circulation and is trapped by reticulo endothelial system (RES) within 6 hours of intraarterial administration. Moreover, an experiment using C3H mouse model revealed that the heat generating capacity of DM is decreased as it is metabolize13EA01 : This is a fundamental study to develop an"intravascular targeting hyperthermia" , in which a deep seated tumor is heated using an intravascularly administered magnetic material together with an externally applied AC magnetic field. As a heat generating material, we employed dextran magnetite complex (DM) , which is a kind of 'magnetic fluid'. The heat production of DM in an AC magnetic field is much higher than previously reported multidomain ferrite particles due to a different mechanism of heat generation. We designed two DM-containing embolic materials, a DM/Lipiodol(]SY.encircledR.[) emulsion and a DM/degradable starch microsphere (DM/DSM) suspension. In vitro experiments showed that the heat generating capacity of DM was not reduced in these preparations. When these materials were injected into the renal arteries of Japanese white rabbits, they achieved selective heating (over 10ﾟC/10min.) of the embolized kidney following exposure to a 100kHz AC magnetic field of approximately 15000 A/m. The average iron concentration in the embolized kidney was 4.9 (]SY.+-.[) 2.4mg Fe/g tissue. A similar experiment with a VX2 tumor transplanted in the liver of a rabbit demonstrated sufficient heating of the tumor. With current composition of DM containing embolic material, DM escapes into systemic circulation and is trapped by reticulo endothelial system (RES) within 6 hours of intraarterial administration. Moreover, an experime Less